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THE 

ENDEMIC  DISEASES 

OF  THE 

SOUTHERN  STATES 


BY 

WILLIAM  H.  DEADERICK,  M.  D. 

T  of  the  Hot  Springs  Medical  Society,  the  Arkansas  Medical  Society,  and  th 
I  Medical  Association ;  JPellow  of  the  American  Medical  Association  and  A 
Society  of  Tropical  Medicine ;  Corresponding  Member  Societe  de  Path- 
ologie  Exotique  (Paris);  Member  of  the  Commission  for   the 
Study  and   Prevention,  of  Malaria;  Secretary  Mala- 
ria Section,  National  Drainage  Congress 


LOYD  THOMPSON,  M.  D. 

Member  of  the  Hot  Springs  Medical  Society,  the  Arkansas  Medical  Society,  and  the  South- 
ern Medical  Association;  Fellow  of  the  American  Medical  Association;  Charter 
Member  of  the  American  Association  of  I  mmunologists ;  First  Lieutenant 
in  the  Medical  Reserve  Corps,  United  States  Army;  Formerly 
Instructor  in  Clinical  Diagnosis  and  Director  of  the 
Clinical  Laboratory,  University  of  Arkansas 


<  (  !■  I'  W.  I:  I  / 

1   l|.|:/.l;V 


ILLUSTRA TED 


PHILADELPHIA  AND  LONDON 

W.  B.  SAUNDERS  COMPANY 

1916 


Copyright,  igiS,  by  W.  B.  Saunders  Company 


J\i4 


PRESS    OF 
SAUNDERS    COMPANY 
PHILADELPHIA 


PREFACE 


The  inception  of  this  book  was  due  to  the  fact  that  there  is 
no  work  in  existence  deahng  solely  with  the  endemic  diseases 
of  the  Southern  States. 

It  must  not  be  inferred  that  the  diseases  considered  are  con- 
fined to  the  states  of  the  South.  On  the  other  hand  most  of 
them  are  disseminated  throughout  the  United  States  and  some 
of  them  are  found  in  most  of  the  states  of  the  Union.  It  is 
true,  however,  that  these  diseases  are  more  prevalent  in  the 
Southern  States. 

It  has  not  been  deemed  advisable  to  treat  of  all  the  diseases 
that  are  especially  prone  to  visit  our  confines  at  longer  or  at 
shorter  intervals  as  the  list  of  such  diseases  is  long  and  such 
a  work  would  necessarily  be  one  on  tropical  diseases  in  general 
to  which  this  work  makes  no  pretension.  We  have  concluded 
that  it  would  be  more  practical  to  consider  intensively  only 
the  endemic  diseases  of  our  Southland  rather  than  to  devote 
brief  space  to  each  of  a  large  number  of  tropical  diseases  the 
most  important  of  which  will  soon  be  of  historic  interest  only. 

Filariasis  which  occurs  in  an  extremely  limited  area  has  been 
omitted. 

We  are  grateful  to  the  publishers  for  courtesies  throughout 
the  publication  of  the  book. 

The  Authors; 

Hot  Springs,  Arkansas, 
March,  igi6. 


13 


CONTENTS 


MALARIA 

WILLIAM  H.  DEADERICK,  M.  D. 

Page 

Chapter         I.  Introduction 17 

Chapter       II.  Etiology 25 

Chapter      III.  Pathologic  Anatomy 90 

Chapter      IV.  Clinical  History 97 

Chapter        V.  Diagnosis 140 

Chapter       VI.  Prognosis 166 

Chapter    VII.  Prophylaxis 172 

Chapter  VIII.  Treatment 197 

BLACKWATER  FEVER 

WILLIAM  H.  DEADERICK,  M.  D. 

Chapter  IX.  Introduction 219 

Chapter  X.  Etiology 229 

Chapter  XI.  Pathology 247 

Chapter  XII.  Clinical  History 250 

Chapter  XIII.  Diagnosis 262 

Chapter  XIV.  Prognosis 265 

Chapter  XV.  Prophylaxis 270 

Chapter  XVI.  Treatment 272 

PELLAGRA 


LOYD  THOMPSON,  Ph.  B.,  M.  D.  and 
WILLIAM  H.  DEADERICK,  M.  D. 

Chapter     XVII.  Introduction 281 

Chapter  XVIII.  Etiology 287 

Chapter      XIX.  Pathology 313 

Chapter        XX.  Clinical  History 324 

Chapter      XXI.  Diagnosis 364 

Chapter     XXII.  Prognosis 379 

Chapter  XXIII.  Prophylaxis 380 

Chapter   XXIV.  Treatment 385 

IS 


i6 


CONTENTS 


AMEBIC  DYSENTERY 

LOYD  THOMPSON,  Ph.  B.,  M.  D.  and 

WILLIAM  H.  DEADERICK,  M.  D. 

Page 

Chapter        XXV.  Introduction 395 

Chapter      XXVI.  Etiology 401 

Chapter    XXVII.  Pathology 413 

Chapter  XXVIII.  Clinical  History • 419 

Chapter      XXIX.  Diagnosis 427 

Chapter        XXX.  Prognosis 434 

Chapter      XXXI.  Prophylaxis 436 

Chapter    XXXII.  Treatment 438 

HOOK-WORM  DISEASE 

WILLIAM  H.  DEADERICK,  M.  D. 

Chapter     XXXIII.  Introduction 445 

Chapter      XXXIV.  Etiology 451 

Chapter       XXXV.  Pathology 460 

Chapter      XXXVI.  Clinical  History 462 

Chapter    XXXVII.  Diagnosis 473 

Chapter  XXXVIII.  Prognosis 478 

Chapter     XXXIX.  Prophylaxis 480 

Chapter               XL.  Treatment 487 

OTHER  INTESTINAL  PARASITES 

WILLIAM  H.  DEADERICK,  M.  D. 

Chapter  XLI.   Other  Intestinal  Parasites 495 

References 528 

Index       541 


ENDEMIC  DISEASES  OF  THE 
SOUTHERN  STATES 


MALARIA 

CHAPTER  I 
INTRODUCTION 

History. — The  history  of  malaria  may  be  traced  to  the  age 
of  fable.  The  story  of  Hercules  and  the  Hydra  is  a  familiar 
one.  This  monster  dwelt  in  the  morasses  in  the  neighborhood 
of  the  Lake  of  Lerna,  where  Hercules  was  dispatched  to  destroy 
him.  As  each  of  the  nine  heads  was  struck  off  two  new  ones 
appeared.  With  the  aid  of  his  faithful  servant,  lolaus,  who 
burned  each  wound  caused  by  the  removed  head,  the  beast 
was  finally  conquered.  Even  before  the  birth  of  Christ  this 
myth  was  construed  to  typify  the  reclamation  of  swamp  lands, 
uninhabitable  on  account  of  the  presence,  of  malaria.  Anti- 
pater  wrote,  "Hercules,  the  greatest  subduer  of  the  foggy 
atmosphere  in  times  past,  was  placed  among  the  Gods  for  hav- 
ing destroyed  the  Hydra;  in  other  words  for  having  reclaimed 
the  marshy  desert."  The  slaying  by  Apollo  of  the  Python 
which  arose  from  the  fertile  ground  after  the  recession  of  the 
flood  is  similarly  interpreted. 

More  than  one  thousand  years  before  the  birth  of  Christ 
malarial  disease  is  mentioned  in  the  Orphic  poems,  and  the 
tertian  and  quartan  types  are  alluded  to.  In  the  Iliad  of 
Homer,  and  the  Wasps  of  Aristophanes  allusions  are  made  to  a 
fever  which  was  probably  malarial.  Paludism  was  probably 
introduced  into  Greece  from  Egypt.  According  to  Groff  the 
word  AAT,  which  is  found  among  the  inscriptions  of  the  temple 
of  Denderah,  referred  to  a  disease,  doubtless  malaria,  which 
recurred  every  year  at  the  same  season. 
2  17 


1 8  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Hippocrates  divided  malarial  fevers  into  continuous  and  in- 
termittent, which  he  subdivided  into  quotidian,  tertian,  and 
quartan.  He  recognized  the  etiologic  influence  of  season,  rains, 
and  stagnant  water,  and  the  dangers  of  malignancy,  dropsy, 
and  affections  of  the  spleen.  Plato  describes  splenic  enlarge- 
ment, and  other  early  Greek  writers  undoubtedly  refer  to 
malaria. 

References  by  Roman  writers  to  malaria  are  not  numerous, 
the  earliest  being  that  of  Plautus,  who  died  184  B.C.  Cato 
speaks  of  "black  bile  and  swollen  spleen,"  and  Cicero,  Varro, 
Celsus,  Livy,  and  others  show  unmistakable  evidence  of  a 
knowledge  of  the  disease. 

Passing  over  the  development  during  the  middle  ages  of  the 
knowledge  of  malaria,  the  names  of  Morton,  Lancisi,  Sydenham, 
and  Torti  appear. 

Morton,  1697,  gave  accurate  clinic  descriptions  of  the  perni- 
cious and  intermittent  fevers,  and  attributed  them  to  miasmatic 
effluvia.  He  was  an  ardent  advocate  of  cinchona  whose  value 
was  at  that  period  being  hotly  contested. 

Sydenham,  1723,  accurately  described  the  malarial  fevers. 
The  intermittent  fevers  he  divided  into  spring  and  autumn 
fevers.  He  justly  concluded  that  the  intermittent  and  con- 
tinuous forms  of  malaria  were  due  to  the  same  cause.  Syden- 
ham ably  defended  cinchona,  and  after  clinic  experiments 
with  its  use,  formulated  useful  rules  for  its  administration. 

Lancisi,  1717,  stated  the  etiologic  relationship  between 
marshy  regions  and  malaria,  and  was  the  first  to  seek  for  a 
microscopic  organism  as  the  cause  of  the  disease. 

Torti,  1753,  wrote  an  exhaustive  treatise  upon  the  various 
forms  of  malaria.  His  classification  of  the  pernicious  forms  has 
become  classical.  Numerous  quotations  from  Torti's"  treatise 
are  to  be  found  even  in  recent  works  upon  malaria. 

Varro,  118-29  B.C.,  expressed  the  opinion  that  malarial 
fever  was  caused  by  animals  so  minute  that  they  could  not  be 
seen  by  the  naked  eye,  and  which  enter  the  body  with  the  air 
through  the  nose  and  mouth.  Similar  opinions  were  held 
by  Columella,  Palladius,  and  Vitruvius.  Rasori  is  quoted  as 
saying,  "For  many  years  I  have  held  the  opinion  that  the 


MALARIA  19 

intermittent  fevers  are  produced  by  parasites  which  renew  the 
paroxysm  by  the  act  of  their  reproduction  which  occurs  more 
or  less  rapidly  according  to  the  variety  of  their  species."  Le 
Diberder,  1869,  maintained  that  the  fever  was  due  to  the 
presence  in  the  blood  of  animals  which  preyed  upon  the  blood, 
and  that  the  paroxysms  depended  upon  reproductive  acts  be- 
tween which  apyrexia  occurred. 

Mitchell,  1849,  claimed  to  have  found  in  the  sputa  of  malarial 
subjects  fungus  spores  in  great  numbers,  which  he  believed  to 
have  been  inspired  with  marsh  air  and  to  have  caused  the 
disease. 

Salisbury,  1866,  announced  the  discovery  in  the  urine  and 
sweat  of  malarial  patients  of  a  species  of  alga,  palmella,  common 
on  the  marshy  regions  along  the  Ohio  and  Mississippi  Rivers, 
which  he  alleged  to  be  the  causative  element. 

Until  the  true  parasite  of  malaria  was  discovered,  the  most 
widely  accepted  parasitic  theory  was  that  proposed  in  1879  by 
Klebs  and  Tommasi-Crudeli.  These  investigators  found  con- 
stantly present  in  the  mud  of  the  Roman  marshes  a  short 
bacillus.  They  were  able  to  cultivate  it  upon  fish  gelatine, 
and  when  injected  into  rabbits  produced  a  fever  similar  to 
malaria.     They  named  it  the  bacillus  malaria. 

The  malaria  parasites  were  undoubtedly  seen  and  described 
before  Laveran  discovered  them.  In  1847,  Meckel,  who  first 
discovered  malarial  pigment,  described  bodies  containing 
pigment  which  correspond  to  the  malarial  parasites.  Virchow, 
in  1849,  ill  3-  description  of  the  pigment,  depicted  cells  now 
known  to  be  parasites,  as  did  also  Frerichs  in  1866.  The 
pigment  was  observed  also  by  Dlauhy,  Heschl,  and  Planer. 
None  of  these  investigators,  however,  recognized  the  significance 
of  these  bodies,  and  their  parasitic  nature  was  not  suspected 
until  1880  by  Laveran,  to  whom  all  the  more  honor  is  due. 

Charles  Louis  Alphonse  Laveran  was  born  at  Paris,  June  18, 
1845.  He  entered  the  mihtary  service  and  was  assigned  to 
Algeria  where  his  brilliant  discovery  was  made  Nov.  6,  1880, 
and  announced  to  the  Paris  Academy  of  Medicine,  Nov.  23, 
1880.  He  was  using  a  one-sixth  inch  dry  lens  when  examining 
the  blood. 


20  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Laveran's  discovery  was  not  accepted  by  the  medical  world 
until  several  years  later;  now  it  has  been  confirmed  the  world 
over.  Among  Americans  who  first  corroborated  Laveran's 
views  may  be  mentioned  Sternberg,  Councilman  and  Abbott, 
Osier,  James,  Dock,  Thayer  and  Hewetson,  Barker,  Woldert 
and  Welch. 

The  discoveries  of  Golgi  in  1885  were  of  great  importance  with 
reference  to  the  hfe  history  of  the  parasite.  He  was  able  to 
follow  tertian  and  quartan  parasites  throughout  the  endogen- 
ous cycle  of  development,  and  showed  that  a  close  relationship 
existed  between  certain  phases  of  parasitic  growth  and  certain 
stages  of  the  paroxysm.  Other  Italian  investigators  proved 
the  same  for  the  estivo-autumnal  parasites. 

A  vague  suspicion  that  malaria  and  mosquitoes  were  in  some 
definite  way  connected  has  been  entertained  in  certain  countries 
for  a  long  period.  A  definite  mosquito  theory,  however,  was 
born  in  America.  While  reference  is  sometimes  made  to  a 
paper  on  the  "Mosquital  Origin  of  Malarial  Disease,"  supposed 
to  have  been  published  by  Dr.  John  Crawford  in  the  Baltimore 
Observer,  in  1807,  no  such  article  has  been  found,  and  the  ref- 
erence is  probably  erroneous. 

In  1848,  Dr.  Josiah  Nott,^^'*  of  Mobile,  published  a  paper  upon 
yellow  fever,  in  which  he  maintained  the  dissemination  of  that 
disease  by  insects,  and  suggested  that  malaria  was  spread  by  the 
"mosquito  of  the  lowlands." 

The  most  complete  theory  was  proposed  by  King,*^°  in  1883. 
His  views  are  supported  by  nineteen  arguments,  most  of  which 
are  incontestable  at  the  present  day. 

That  mosquitoes  are  agents  in  the  spread  of  malaria  was 
advanced  by  Koch  in  1884,  by  Laveran  in  1884,  by  Flugge  in 
1891,  by  Manson  in  1894,  and  by  Bignami  in  1896. 

Undertaking  the  work  of  Manson's  suggestion,  and  after 
several  years  (1895-1898)  of  toil  and  discouragement,  Ross 
proved  conclusively  that  certain  species  of  mosquitoes  were 
concerned  in  the  dissemination  of  malaria.  The  debt  owed 
him  by  mankind  was  acknowledged  by  the  gift  of  a  Nobel  prize. 

MacCallum  in  1898  demonstrated  that  the  flagella  represent 
male  sexual  elements  analogous  to  spermatozoa. 


Bass'  discovery  of  the  method  of  cultivating  the  malarial 
parasites  is  the  most  important  landmark  in  the  history  of 
malaria  since  the  discovery  of  Ross. 

Geographic  Distribution. — North  America. — In  the  United 
States  it  is  chiefly  the  southeastern  portion  in  which  malaria  is 
most  prevalent.  Along  the  Atlantic  Coast,  south  of  New  York 
and  especially  the  lowlands  of  Maryland  and  Virginia,  and  in 
the  Carolinas,  Georgia  and  Florida  the  disease  occurs  frequently. 
Along  the  Gulf  coast  and  up  the  Mississippi  River  and  its  tribu- 
taries, malaria  is  widely  prevalent.  The  portions  of  the  States 
lying  along  the  Appalachian  Range  are  almost  exempt,  but  the 
disease  appears  as  the  Mississippi  River  and  the  Atlantic  Coast 
upon  either  side  are  approached.  West  of  the  Mississippi, 
Arkansas,  Louisiana,  and  Texas  present  the  most  numerous  foci 
of  malaria.  In  portions  of  Pennsylvania  and  New  York  au- 
tochthonous cases  are  not  infrequently  observed.  In  the  more 
southern  New  England  States  malaria  is  still  encountered,  and 
in  some  places  is  even  increasing  in  frequency.  In  the  neighbor- 
hood of  the  Great  Lakes  malaria  is  very  rare,  excepting  possibly 
that  of  Lake  Erie  and  of  Lake  Michigan.  In  the  Central  States 
malaria  has  almost  or  quite  disappeared,  except  in  certain  low 
river  valleys.  Along  the  Pacific  Coast  the  disease  is  not  so 
frequent  as  along  the  Atlantic.  In  Washington  it  occurs  in  the 
Puget  Sound  Basin  and  the  Columbia  River,  Chehalis,  and  the 
Yakima  valleys.  In  Oregon  malaria  is  found  in  the  Columbia, 
Williamette,  Rogue,  and  the  Umatilla  valleys,  and  in  California 
in  the  Sacramento,  San  Joaquin,  Tulare,  Kern,  and  Santa  Clara 
valleys.  In  certain  parts  of  New  Mexico  malaria  is  occasion- 
ally met  with. 

Canada  is  free  from  paludism  except  along  the  northern  shore 
of  Lake  Ontario. 

In  Mexico  severe  forms  of  malaria  occur,  particularly  in  the 
low  coast  regions. 

Malaria  abounds  in  Central  America  along  the  Atlantic 
Coast  and  to  a  less  extent  upon  the  Pacific  side. 

South  America. — The  eastern  coast  of  South  America  is  more 
intensely  infested  with  malaria  than  is  the  western  coast. 
Venezuela  (in  the  valleys),  Guiana,  and  the  greater  portion  of 


2  2  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Brazil  are  highly  malarial.  Portions  of  Paraguay  and  of 
Bolivia  afford  a  great  many  cases,  while  the  disease  is  much  less 
prevalent  in  Uruguay  and  almost  absent  from  the  Argentine 
Republic.  On  the  Pacific  border  the  deep  valleys  of  Peru  and 
of  Ecuador  are  malarial  centers. 

The  entire  island  of  Cuba  is  malarial  to  a  greater  or  less  ex- 
tent, as  is  also  Jamaica.  Of  the  Lesser  Antilles,  St.  Vincent 
and  Antigua  are  highly  malarial,  and  Barbadoes  is  exempt. 
Malaria  is  said  to  be  almost  unknown  in  the  Bermudas. 

Europe. — Great  Britain,  once  infested,  is  now  free  from  en- 
demic malaria.  In  Germany  the  disease  occurs  infrequently 
in  the  Rhine  and  Danube  valleys  and  near  the  mouths  of  rivers 
along  the  coast.  Malaria  is  met  in  Holland,  chiefly  upon  the 
island  of  Zeeland  and  in  North  and  South  Holland.  The  valley 
of  the  Danube,  in  Austria,  affords  a  considerable  number  of 
cases.  There  are  a  few  regions  in  Hungary  in  which  the  disease 
does  not  occur,  but  it  is  especially  along  the  western  half  of  the 
southern  border  that  it  is  prevalent.  The  marshes  along  the 
west  coast  and  the  south  of  France  give  rise  to  a  number  of  cases 
of  malaria.  In  Spain  and  Portugal  malaria  occurs  in  the  coast 
regions  and  in  the  larger  river  valleys.  The  disease  is  practi- 
cally unknown  in  Norway,  but  is  occasionally  reported  from 
Sweden,  as  well  as  from  certain  of  the  islands  of  Denmark.  In 
Russia  it  is  in  the  southern  portion,  particularly  along  the  coasts 
and  along  the  valleys  of  the  rivers  flowing  southward,  that 
malaria  is  encountered.  Cases  are  occasionally  observed  in  the 
southwest  of  Switzerland.  The  portions  of  Bulgaria  most 
highly  malarial  are  the  Danube  valley,  the  coast  region,  and  the 
southern  part.  Almost  the  whole  of  Italy  is  sorely  afflicted  with 
malaria,  as  are  also  Sicily  and  Sardinia.  Greece  is  the  most 
severely  scourged  country  of  Europe.  It  is  said  that  in  the 
plains  of  Thessaly,  Phthiotis,  Acarnania,  Boeotia,  Elis,  Mes- 
senia,  Argos,  and  Laconia  hardly  a  single  inhabitant  escapes 
the  disease. 

Asia. — Asia  Minor,  Arabia,  and  Persia  present  foci  of  malaria, 
both  in  the  coast  neighborhoods  and  in  the  interior  lowlands. 
In  the  swampy  regions  of  Afghanistan  and  Beloochistan 
malaria  is  common  and  severe.     The  foothills  of  the  Himalayas, 


MALARIA  23 

the  Duars,  and  Terai  are  famous  malaria  seats.  Both  the  coast 
regions  and  the  interior  highlands  of  Ceylon  are  endemic 
territory.  Burmah,  Siam,  the  Malay  Peninsula,  and  French 
Indo-China  are  malarial  in  portions  of  their  extent,  and  parts  of 
China  are  intensely  infested.  Malaria  is  found  in  Japan, 
Formosa,  and  the  PhiHppines,  and  portions  of  the  East  Indies 
are  among  the  most  highly  malarial  regions  of  the  world. 

Africa. — On  the  west  coast  the  territory,  between  the  Senegal 
and  the  Congo  Rivers,  is  headquarters  for  malaria  of  malignant 
type.  Approaching  South  Africa  the  disease  diminishes  in 
frequency  and  in  severity.  On  the  east  the  region  from  Delagoa 
Bay  to  Eritrea  is  malarial.  In  the  interior  of  Central  Africa, 
excepting  the  high  elevations,  malaria  is  widespread.  Malaria 
abounds  in  Madagascar,  excepting  upon  the  northeast  coast 
and  the  mountainous  interior.  Reunion  and  Mauritius  are  also 
malarial.  In  Egypt  it  is  chiefly  the  region  overflowed  by  the 
Nile  in  which  the  disease  is  most  prevalent.  Malaria  abounds 
about  the  coasts  and  marshes  of  Algeria. 

In  Australia  malaria  occurs  from  Cape  York  to  Brisbane,  on 
the  east  coast,  diminishing  toward  the  south.  New  Zealand 
is  apparently  free  from  malaria,  and  the  Sandwich  Islands  and 
most  of  the  other  Pacific  islands  are  markedly  exempt. 

The  relative  frequency  of  the  forms  of  malarial  infection 
varies  greatly.  It  may  be  stated  as  a  general  proposition  that 
the  quartan  is  the  rarest  form,  the  tertian  is  the  form  prevailing 
in  temperate  regions,  and  the  estivo-autumnal  in  warm  and  hot 
climates.  There  are  regions,  however,  in  which  the  quartan 
predominates,  as  in  certain  portions  of  Italy  and  of  India;  in 
other  localities  it  is  the  only  form  of  malaria  present,  as  upon 
the  island  of  Merite,  of  the  Bismarck  Archipelago. 

The  following  table  shows  the  relative  frequency  of  the  types 
of  malaria  in  various  regions : 


24 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


Authority 


Texas 

Georgia 

Camp  WikofE 

New  Orleans 

Baltimore 

Panama 

St.  Lucia 

Panama 

Italy 

Italy 

Greece 

Bulgaria 

Italy 

British  Malaya 

British  Malaya 

Philippines 

India 

Cyprus 

East  Indies 

Philippines 

India 

India 

Assam 

Japan 

Togo 

German  East  Africa 
German  East  Africa 

Senegal 

German  East  Africa 
German  East  Africa 
German  East  Africa 
German  East  Africa 


Moore"" 

Curry"' 

Ewing'^ 

Charity  Hospital  Recs.'"* 

Thayer  and  Hewetson'"' 

Kendall"" 

Gray  and  Low*" 

Gorgas"2 

Koch"3 

Koch"* 

Cardimatis  and  Diamessis"^ 

MoUow"6 

Italian  statistics'''" 

Wright"* 

Watson"' 

Craig"' 

Hope"" 

Williamson"'- 

Koch'"2 

Chamberlain*'^' 

Rogers" 

Buchanan''" 

Bentley''** 

Tsuzuki''" 

Ziemann*' 

Meixner'' 

Grothusen" 

Thiroux  and  d'Antreville"" 

Kudicke" 

Exner'' 

OUwig'i 

Schornich'^ 


23 
34 

74 
373 
338 


4,012 

32 
202 


32,392 

78 

19 

98 

217 

12 

S7 

55 

1.372 

56 

134 

345 

I 

5 

5 

7 

3 


119 

3 
71 


30 

16 
261 
203 
188 
291 
109 
10,815 

78 
191 
145 

67 

23,520 

117 

28 

272 

547 

4 

123 

62 

1,311 

118 

74 
107 

32 
102 

68 
266 
118 
328 
134 
130 


CHAPTER  n 

ETIOLOGY  OF  MALARIA 

Malaria  is  of  very  complex  etiology,  depending  as  it  does  for 
its  existence  upon  the  life  histories  of  three  species  of  animals. 
While  within  the  blood  of  man  the  parasite  is  not  subject  to 
great  variations  of  environment,  no  matter  what  the  season  or 
the  latitude,  nevertheless  exposure  to  cold,  wet  or  heat, 
dietary  or  other  excesses,  will  have  the  effect  of  awakening 
latent  malaria. 

But  it  is  the  influence  of  external  factors  upon  the  life  history 
of  the  mosquito  that  determines  the  greatest  variations  in  the 
prevalence  of  malaria  according  to  climate,  season,  temperature, 
rainfall,  altitude,  etc. 

Climate. — It  may  be  said  as  a  general  rule,  that  the  frequency 
and  virulence  of  malaria  increase  as  we  approach  the  equator. 
The  conditions  of  warmth  and  moisture  are  more  propitious  for 
the  development  of  the  parasites  within  the  bodies  of  mosquitoes 
in  tropic  than  in  colder  climates;  this  is  especially  true  of  the 
estivo-autumnal  form  of  the  malarial  parasite.  Exposure  to 
the  heat  of  the  tropical  sun  predisposes  to  the  cerebral  forms  of 
pernicious  malaria,  and  undue  exposure  to  the  sun's  rays  is 
ofttimes  sufficient  to  stimulate  sporulation  of  the  parasites  of 
latent  malaria. 

With  respect  to  latitude  Hirsch^"  reached  the  following 
conclusions  as  to  the  northern  boundary  of  malaria  in  the 
northern  hemisphere.  The  line  starts  from  55°N.  on  the 
western  side  of  North  America,  sinks  to  45°  on  its  eastern  side, 
rises  to  63°  or  64°  on  the  western  side  of  the  old  world  (Sweden 
and  Finland),  and  runs  across  Northern  Asia  in  about  the 
latitude  of  55°. 

Long  before  the  discovery  of  the  role  of  the  mosquito  in 
malaria  it  was  known  that  the  disease  was  not  endemic  unless 
the  summer  temperature  maintained  a  certain  average.  Hirsch 
maintained  that  the  summer  isobar  of  S9°-6o.8°F.  marks  the 

25 


26  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

limit  of  the  occurrence  of  malarial  fever,  and  that  those  regions 
where  the  mean  summer  temperature  does  not  reach  that 
height  are  exempt  from  the  disease.  Curiously  enough,  it 
has  been  recently  repeatedly  demonstrated  that  this  is  the 
lowest  temperature  at  which  the  parasite  wiU  develop  in  the 
body  of  the  mosquito. 

Season. — While  relapses  may  occur  at  any  season,  and  in 
certain  tropic  regions  fresh  infections  may  occur  during  any 
period  of  the  year,  in  all  temperate  and  most  tropic  regions 
there  are  seasons  during  which  the  disease  is  especially 
prevalent.  This  is  commonly  known  as  the  malarial  season, 
and  varies  according  to  latitude,  temperature,  rainfall,  soil,  etc. 

The  season  of  primary  attacks  depends  entirely  upon  the 
Ufe-history  of  the  malaria-bearing  mosquitoes.  This  season 
usually  begins  a  few  weeks  after  the  first  brood  of  anophehnes 
appears,  which  is  at  the  height  of  summer,  and  continues,  in 
temperate  chmates,  until  after  the  nights  become  cool.  In 
each  individual  locality  the  beginning  of  the  season  is  rather 
definite,  the  disease  recurring  at  a  certain  period  each  year 
with  more  or  less  exactitude.  In  most  of  the  regions  of  the 
Southern  States  the  malarial  season  begins  in  the  earlier  half 
of  July.  In  the  latitude  of  Baltimore  the  most  notable  increase 
in  cases  begins  during  August.  The  malarial  season  in  Cali- 
fornia is  from  August  to  October. 

Where  both  tertian  and  estivo-autumnal  malaria  are  endemic, 
the  malarial  season  is  usually  ushered  in  by  cases  of  the  former, 
the  estivo-autumnal  variety  appearing  at  the  height  of  the 
season.  The  pernicious  forms  of  malaria  occur  with  greatest 
frequency  at  the  height  of  estivo-autumnal  prevalence.  In 
Italy  quartan  malaria  begins  late  in  the  summer  and  continues 
late  in  the  fall.  In  America  this  variety  is  too  infrequent  to 
justify  any  definite  conclusions.  Mixed  and  multiple  infections 
occur  more  frequently  late  in  the  season  than  early. 

Rainfall. — The  influence  of  rainfall  upon  the  extent  of  malaria 
is  very  decided.  Breeding  places  for  mosquitoes  are  essential 
in  the  etiology  of  malaria,  and  limited  pools,  such  as  result 
from  a  fall  of  rain,  are  well  suited  to  the  taste  of  the  malarial 
mosquitoes. 


MALARIA  2  7 

Rain  has  a  twofold  effect  upon  the  prevalence  of  malaria. 
First,  exposure  to  wet  is  not  infrequently  followed  by  a  re- 
crudescence of  a  former  infection.  This  effect  is  usually 
immediate.  Second,  rainfall  produces  breeding  pools  for  the 
disseminators  of  malaria.  The  effect  of  fresh  breeding  places 
is  not  shown  immediately.  Allowing  twenty  days  for  the 
aquatic  stages  of  the  mosquito,  ten  days  for  the  mosquito  cycle 
of  the  parasite,  and  a  Hke  period  for  the  incubative  stage  in 
man,  it  would  be,  obviously,  several  weeks  before  an  increase 
in  malaria  could  be  expected  from  such  a  source.  This  is  well 
exempUfied  in  the  tropics,  where  so  much  depends  upon  rainfall. 
Here  the  height  of  the  malaria  curve  is  attained  toward  the  end 
of  the  rainy  season,  or  shortly  after. 

A  heavy  rainfall  in  the  spring  and  early  summer  has  long  had 
the  reputation  of  being  favorable  to  the  spread  of  malaria. 

While  rainfall  is  essential  to  the  development  of  malaria,  if 
excessive  it  may  have  the  opposite  effect  by  scouring  breeding 
pools  and  destroying  the  contained  ova  and  young  of  the 
mosquito.  Moderate  rains  at  short  intervals  are  more  pro- 
ductive of  breeding  pools  than  heavy  downpours  at  long 
intervals.  Hence,  the  number  of  rainy  days,  as  well  as  the 
actual  rainfall  in  inches,  is  a  factor  in  the  etiology  of  malaria. 

In  very  low  countries  rainy  years  may  be  healthy  years. 
This  is  said  to  be  the  case  in  the  Netherlands. 

Dew  and  a  high  atmospheric  moisture  were  formerly  ac- 
credited with  being  factors  in  the  cause  of  malaria.  This  was 
doubtless  on  account  of  the  well-recognized  danger  of  contract- 
ing malaria  between  sunset  and  sunrise.  Other  than  as  an 
index  of  ground-moisture  it  is  doubtful  whether  atmospheric 
moisture  bears  any  relation  to  primary  infections  with  malaria. 

Soil. — The  chemical  composition  of  the  soil  has  an  effect 
upon  the  reign  of  malaria  only  so  far  as  the  relation  of  the  soil 
to  the  retention  of  water  is  concerned.  More  depends  upon 
the  physical  conformation  than  upon  the  geologic  characteristics 
of  the  soil.  As  a  rule,  clay  soils  retain  moisture  better  than  the 
sandy,  though  there  are  exceptions.  Rocky  regions  are  less 
apt  to  harbor  breeding  pools  because  of  good  drainage,  but  pools 
upon  a  rock  bed  are  very  persistent.     The  soil  must  be  of  such  a 


28  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

character  as  to  retain  surface  water  sufi&ciently  long  for  the 
aquatic  stages  of  mosquito  life  to  be  completed. 

More  depends  upon  the  nature  of  the  subsoil  than  upon  that 
of  the  surface  soil.  Even  where  the  surface  soil  is  very  porous, 
an  impervious  subsoil  favors  the  accumulation  of  surface  water 
by  preventing  further  percolation.  Thus  the  height  of  the 
ground-water  during  the  malarial  season  bears  a  close  relation 
to  the  volume  of  the  malarial  endemic.  Proximity  to  collec- 
tions of  water,  by  raising  the  height  of  the  ground-water,  favors 
the  development  of  malaria. 

Topography. — In  countries  designated  malarial,  regions 
entirely  free  from  the  disease  are  not  uncommon.  In  a  region 
within  a  short  distance  of  a  severely  scourged  locality  malaria 
may  be  entirely  absent.  The  difference  in  the  prevalence  of 
malaria  within  limited  areas  is  dependent,  in  great  measure, 
upon  the  physical  characteristics  of  the  surface  of  the  land. 

It  has  been  known  for  centuries  that  malaria  is  partial  to  low 
marshy  places,  swamps,  lakesides,  low  coast  levels,  and  river 
valleys,  and  especially  the  deltas  of  large  rivers.  The  cleaner 
the  banks  and  the  swifter  the  current  of  the  streams  at  all  stages 
the  less  apt  they  are  to  be  malarious.  Streams  with  sluggish 
or  no  currents,  and  with  weedy  banks  which  foster  eddies,  are 
breeding  places  for  mosquitoes. 

It  is  generally  believed  that  salt  marshes  are  never  malarious, 
and  that  anopheles  larvae  cannot  develop  in  sea- water.  This  is, 
however,  not  strictly  true.  DeVogeP^^  has  recently  shown  that 
anopheles  larvae  may  develop  in  sea-water  evaporated  to  half 
its  initial  volume,  and  a  number  of  other  observers  have  found 
larvae  in  salt  water.  But  marshes  of  pure  sea-water  are  not 
nearly  so  noxious  as  those  of  brackish  water,  a  mixture  of  salt 
and  fresh  water,  which  are  famous  anopheles  breeders.  It 
appears  that  in  some  instances,  where  salt  water  is  inimical  to 
the  development  of  the  aquatic  stages  of  mosquitoes,  they  may 
gradually  become  accustomed  to  the  environment. 

Altitude. — Malaria  is  essentially  a  disease  of  the  lowlands, 
high  altitudes  being  relatively  exempt.  This  is  partially  ac- 
counted for  by  the  better  drainage  of  elevated  altitudes  and 
fewer  pools  in  which  malarial  mosquitoes  may  breed.     The 


MALARIA  29 

lower  temperature  of  high  altitudes  is  also  a  factor  in  maintain- 
ing a  low  malarial  morbidity  in  these  regions. 

It  is  known  that  anophehne  mosquitoes  do  not  fly  to  great 
heights.  Hence  sleeping  in  an  upper  story  or  in  a  building 
situated  high  above  the  ground  gives  a  measure  of  protection 
from  malaria.  Laborers  employed  in  highly  malarial  sections, 
and  who  sleep  in  the  surrounding  hills,  even  of  moderate  alti- 
tude, often  remain  entirely  free  from  infection. 

A  few  hundred  feet  in  altitude  may  show  a  more  marked 
difference  in  the  prevalence  of  malaria  than  as  many  miles  in 
latitude. 

The  general  rule  that  malaria  is  a  disease  of  low  countries  has 
some  exceptions.  This  is  especially  true  in  the  tropics,  where 
the  disease  may  be  encountered  at  very  high  altitudes.  It  may 
be  said  that  the  altitude  at  which  malaria  may  occur  varies  in 
inverse  ratio  to  latitude. 

Malaria  has  been  found  on  Lake  Nyssa  at  an  altitude  of 
1,560  meters;  at  Colico,  2,500  meters;  in  the  Himalaya  Moun- 
tains, at  2,000  meters;  in  the  Andes,  at  2,500  meters;  at  Blan- 
tyre,  at  3,000  feet;  German  East  Africa,  at  1,550  meters;  at 
points  in  Central  Africa,  at  heights  of  over  5,000  feet;  and  in 
some  of  the  high-lying  valleys  of  Syria,  at  altitudes  of  1,200 
meters. 

Some  of  the  cases  in  high  altitudes  reported  as  malaria  may 
be  mistakes  in  diagnosis;  other  cases  may  be  malaria  contracted 
in  the  lowlands.  Thus  Tosari,  at  an  elevation  of  1,177  meters, 
has  been  cited  as  a  place  where  malaria  prevailed  without  the 
presence  of  mosquitoes,  and  this  was  used  as  an  argument 
against  the  "mosquito  theory."  Koch,'-^  investigating  the 
place  in  1899,  examined  the  blood  of  eighty- two  children; 
in  none  was  the  parasite  of  malaria  detected.  The  only  case 
of  malaria  found  was  in  a  man  who,  twelve  days  before  the 
beginning  of  his  illness,  had  spent  the  night  in  a  highly  malarial 
place  upon  the  coast. 

However,  malaria  is  endemic  in  certain  places  of  high  altitude. 
Such  are  Eritrea,  in  altitudes  of  1,750  meters;  Upper  Tonkin,  at 
1,000  meters;  parts  of  Madagascar,  at  1,100  meters;  parts  of 
Reunion  Island,  1,200  meters;  in  Java,  at  1,000  meters;  and  in 


30  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

the  Philippines  it  is  said  that,  while  certain  valleys  are  almost 
free  from  malaria,  the  hills  in  the  vicinity  are  notoriously  in- 
fected. Wright,'*''^  in  British  Malaya,  found  anopheles  larvae  in 
pools  at  an  elevation  of  2,300  feet. 

Earthquakes  and  volcanic  eruptions  have  been  followed  by  a 
great  development  of  malaria.  Examples  are  cited  of  Rome  in 
1703,  in  Reggio  in  1783,  and  Palermo  in  1828.  Remarkable 
instances  have  occurred  in  Peru  also.  The  most  recent 
illustration  is  that  of  Amboina,  in  the  East  Indies,  which  had 
until  183  s  been  remarkably  free  from  malaria.  In  that  year  a 
severe  earthquake  occurred,  and  since  then  the  malaria  has 
increased  both  in  extent  and  intensity. 

Such  results  can  be  explained  only  by  an  increase  of  stagnant 
water  following  these  violent  disturbances,  probably  through 
the  interruption  of  the  flow  of  ground-water. 

Invmdations. — Since  very  early  times  overflows  have  been 
recognized  as  a  prolific  cause  of  epidemics  of  malaria.  Tacitus, 
Suetonious,  Livy,  Dionysius,  Cassio,  and  Strabo,  mention  such 
results  from  inundations  of  the  Tiber.  This  stream  experienced 
an  overflow  in  1695,  which  was  described  by  Lancisi.  The 
water  covered  a  broad  area  of  country,  filling  ditches,  sewers  and 
canals.  The  following  June,  July  and  August  were  extremely 
hot.  An  epidemic  of  malignant  malarial  fever  ensued  and, 
spreading  far  and  wide,  occasioned  a  great  mortality. 

Epidemics  of  malaria  following  overflows  of  the  Nile,  Ganges, 
Indus,  Euphrates,  Niger,  Senegal,  Volga,  Danube,  Saone, 
Rhone,  Loire,  Mississippi,  and  other  rivers  have  been  described. 

The  immediate  effect  of  an  inundation  is  to  check  the  devel- 
opment of  malaria.  This  is  a  result  of  a  destructive  effect  of  the 
flood  upon  the  breeding  pools  of  mosquitoes.  It  is  only  after 
the  waters  have  subsided  and  pools  and  marshes  are  left  that 
the  epidemic  develops. 

Trees  and  Vegetation. — It  was  formerly  beheved  that,  while 
decaying  vegetation  was  the  cause  of  malaria,  living  plant  life 
greatly  retarded  its  development.  Whole  volumes  have  been 
devoted  to  this  subject.  It  was  supposed  that  vegetation  filtered 
the  miasm  from  the  air.  It  was  argued  that  if  air  vitiated  by 
respiration  be  confined  in  a  bottle  containing  a  living  plant 


MALARIA  3 1 

and  exposed  to  the  rays  of  the  sun,  the  carbonic-acid  gas  will  be 
absorbed  and  the  air  restored  to  its  original  condition,  plant 
life  consuming  carbon  dioxide  and  exhaling  oxygen.  So  firm 
was  this  belief  that  in  the  days  of  ancient  Rome  trees  were 
protected  by  law. 

It  is  needless  to  say  that  the  protective  power  of  living  plants 
was  as  much  overestimated  as  the  faculty  of  decaying  vegetation 
to  cause  malaria.  Their  power  of  absorbing  moisture  from  the 
soil  is  more  than  outweighed  by  the  shade  they  afford  the  ground. 

While  the  clearing  of  land  of  trees  and  vegetation  may  be 
followed  by  an  outbreak  of  malaria,  this  may  be  due  to  the  over- 
turning of  the  soil,  which  usually  goes  hand  in  hand  with  open- 
ing land,  and  to  the  hardships  attending  such  labor.  The  ulti- 
mate effect  of  clearing  trees  from  the  land  is  to  diminish  malaria 
by  permitting  the  sun  to  dry  the  soil. 

If  trees  have  any  protective  virtues  whatever,  it  is  probably 
through  affording  shelter  and  food  for  mosquitoes.  The 
culture  of  eucalyptus  trees  is  now  known  to  have  no  prophylac- 
tic effect  upon  malaria. 

Weeds  and  other  vegetation  growing  in  the  water  favor  the 
development  of  mosquito  larvffi  by  protecting  the  surface  of  the 
water  from  agitation  by  the  wind. 

Vegetable  decomposition  bears  no  relation  to  the  etiology 
of  malaria  other  than  as  an  index  to  heat  and  moisture. 

Wind. — The  wind  was  formerly  held  responsible  for  trans- 
mitting malaria  long  distances.  It  was  believed  that  the  malaria 
of  Edinburgh  was  imported  by  the  winds  from  Holland,  and 
that  Italy  became  malarious  through  the  agency  of  the  African 
sirocco.  The  land  breezes,  especially  if  they  blew  over  marshy 
areas,  were  regarded  as  more  highly  noxious  than  the  sea 
breezes. 

As  a  matter  of  fact,  the  wind  has  little  or  no  power  to  transmit 
malaria  for  distances  of  any  consequence.  While  it  is  theoret- 
ically possible  for  infected  mosquitoes  to  be  borne  by  the  wind, 
in  reality  these  insects,  especially  the  anopheles,  being  weak 
fliers,  seek  shelter  while  a  breeze  is  blowing.  The  immunity 
from  mosquito  bites  afforded  by  the  Indian  punkah,  or  a 
common  fan,  is  evidence  of  this. 


32  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Furthermore,  the  disturbing  effect  of  the  wind  upon  the  sur- 
face of  the  water  interferes  with  oviposition  of  the  adults  and 
with  respiration  of  larvae  and  pupae. 

Exposure  to  cold  winds  may  have  the  effect  of  arousing  latent 
malaria. 

The  occurrence  of  malaria  upon  shipboard  has  been  cited 
as  an  argument  that  malaria  is  an  air-born  disease.  Bilge 
water  in  the  holds  of  vessels  has  also  been  accredited  with  pro- 
ducing malaria  at  sea. 

Malaria  occurring  upon  ships  may  be  accounted  for  in  several 
ways.  These  cases  may  be  manifestations  of  malaria  contracted 
upon  shore.  Even  cases  occurring  long  after  embarking  may 
be  explosions  of  latent  malaria.  If  vessels  anchor  too  close  in 
shore  in  malarial  regions  infected  mosquitoes  may  easily  gain 
access  to  the  crew — a  half  mile  from  shore  is  probably  a  safe 
distance.  It  has  been  proven  that  mosquitoes  may  be  carried 
for  considerable  periods  in  the  holds  and  sleeping  apartments  of 
ships. 

There  are  many  places  where,  notwithstanding  apparently 
favorable  topographic  and  meteorologic  conditions,  malaria 
is  entirely  absent.  This  is  due  to  the  absence  of  either  malaria- 
bearing  mosquitoes,  or  malarial  parasites,  or  of  both.  Among 
a  number  of  such  places  may  be  mentioned  the  city  of  Rome  and 
other  portions  of  Italy,  Madeira,  portions  of  Cameroon,  Chole 
Islands,  portions  of  India  and  of  Borneo,  the  French  Islands, 
Ponape,  Saipan,  Samoa,  New  Caledonia,  Tahiti,  Barbadoes, 
and  portions  of  Brazil  and  of  the  Argentine  Republic.  The 
majority  of  such  localities  are  islands  and  in  the  southern 
hemisphere. 

Race;  Immunity. — Certain  protozoan  diseases  among  lower 
animals  confer  immunity.  In  the  Texas  fever  of  cattle  an 
attack,  if  recovered  from,  is  followed  by  immunity.  There  are 
said  to  be  breeds  of  cattle  naturally  immune  to  the  disease. 
In  the  large  game  animals  of  Africa  one  infection  with  try- 
panosoma  brucei  confers  immunity.  Koch  found  that  birds 
that  had  been  infected  with  proteosoma  grassii  could  not  be 
reinfected. 

From  analogy  it  might  therefore  be  expected  that  immunity 


MALARIA  33 

to  malaria  might  exist  with  some  individuals  or  races.  This 
is  true,  however,  in  only  a  limited  sense. 

While  the  various  races  of  mankind  vary  somewhat  in  sus- 
ceptibility to  malaria,  none  can  be  said  to  possess  absolute 
immunity. 

Caucasians  residing  in  non-malarial  countries  are,  when 
exposed,  most  liable  to  contract  malaria.  Negroes  bred  in 
highly  malarial  regions  are,  as  long  as  they  remain  upon  the 
native  soil,  least  susceptible  to  paludal  infection. 

Immunity  within  the  race  increases  generally  as  we  go  toward 
the  equator.  Thus  the  negroes  of  the  Southern  States  display 
less  immunity  than  the  negroes  of  the  West  Indies  or  of  tropic 
Africa.  Likewise  it  may  be  said  that  immunity  is  much  more 
marked  in  countries  with  a  high  than  in  those  with  a  low 
endemic  index. 

The  immunity  of  the  negro  race  has  been  variously  estimated, 
some  observers  maintaining  that  they  are  absolutely  proof 
against  malarial  invasion,  while  others  hold  that  they  are  as 
susceptible  as  the  whites.  The  truth  lies  between  these  two 
extremes.  Adult  negroes  reared  in  malarial  regions  are  much 
less  liable  to  paludism,  as  long  as  they  remain  indigenous,  than 
are  the  whites.  The  negro  race  does  not,  however,  enjoy  an 
absolute  but  only  a  relative  immunity  from  malaria. 

According  to  Sternberg,^^^  there  were  in  the  department 
of  Texas  of  the  United  States  Army  during  the  year  ending 
June  30,  1883,  among  the  white  soldiers  21.36  per  cent.,  colored, 
6.27  per  cent,  of  periodic  fevers  to  all  kinds  of  fevers. 

Sternberg*"^  gives  the  ratio  per  thousand  of  mortality  from 
malarial  diseases  in  the  United  States  Army  thus: 


1868 

1869 

1S70 

White 

94.20 
74.62 

140.67 
15.62 

72.99 
38.46 

Colored 

During  the  Civil  War  both  the  morbidity  and  the  mortality 
from  malaria  in  the  negro  race  were  greater  than  in  the  white 
race.     However,  the  negro  soldiers  are  said  to  have  been  more 
3 


34 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


exposed  to  malaria  than  the  whites,  having  been  aggregated  in 
malarial  locahties. 

With  the  better  hygienic  surroundings  and  more  limited 
exposure  of  the  whites  the  negroes  would  probably  be  attacked 
less  often  than  they  are.  Whether  the  color,  thickness,  or 
other  qualities  of  the  skin  of  this  race  have  anything  to  do  with 
relative  immunity  is  not  known. 

At  Stephansort,  Koch*^^  found  various  races  infected  in  the 
following  proportions: 


Number  infected  with 


Europeans. . 

Chinese 

Malays 

Melanesians 

Total 


240 
209 
264 


12 

S7-I 

63 

26.3 

53 

25 -3 

29 

10. 9 

Immunity  from  malaria  is  probably  an  acquired  immunity 
in  the  great  majority  of  instances,  though  the  contrary  opinion 
is  held  by  some  competent  authorities  upon  the  subject.  The 
reasons  for  believing  that  this  immunity  is  acquired  by  re- 
peated infection,  especially  in  childhood,  and  by  prolonged 
residence  in  a  malarial  region,  a  sort  of  acclimatization,  are,  that 
immunity  is  much  more  prevalent  in  adults  than  in  children; 
that  immunity  is  often  diminished  by  a  change  of  resi- 
dence or  may  be  entirely  lost  by  a  temporary  residence 
in  a  nonmalarial  climate;  and  that  immunity  in  an  individ- 
ual may  exist  toward  one  form  of  malaria  and  not  toward 
others. 

That  immunity  is  much  more  manifest  in  adults  than  in 
children  is  evident  from  the  consideration  of  the  endemic  index 
of  malarial  regions,  particularly  of  countries  where  the  latter 
is  high.  During  the  first  years  of  life  many  individuals  ex- 
amined show  evidence  of  malarial  infection,  older  children 
in  a  less  proportion,  and  adults  evince  a  relative  immunity. 
This  would  hardly  be  the  case  if  the  immunity  were  racial  and 
congenital. 


MALARIA  35 

The  effect  of  a  change  of  residence  upon  malarial  immunity  is 
a  well-known  fact.  Plehn^  says  that  the  Soudan  negroes, 
relatively  immune  at  home,  are  often  afiflicted  with  malaria  when 
going  as  soldiers  to  other  parts  of  the  continent.  Smith''*'' 
states  that,  while  the  native  negroes  of  Sierra  Leone  are  in- 
frequently attacked,  and  only  with  mild  degrees  of  malaria,  in 
the  West  Indies  regiment  of  negroes  stationed  in  Sierra  Leone 
the  fever  is  of  a  severe  and  often  fatal  character. 

Individuals  once  immune  to  malaria  may  become  susceptible 
on  returning  home  from  a  temporary  residence  in  a  malaria- 
free  country.  Plehn^  mentions  three  Cameroon  negroes  who, 
shortly  after  returning  from  a  several  years'  sojourn  in  Europe, 
were  attacked  with  severe  remittent  fever. 

Repeated  infection  and  consequent  immunity  to  one  form  of 
malaria  does  not  usually  protect  the  individual  from  the  other 
forms. 

In  the  South  there  is  Httle  difference  between  the  races  as 
regards  susceptibility  to  the  various  forms  of  malarial  infection 
— tertian,  quartan,  and  estivo-autumnal.  Clinically,  however, 
pernicious  cases,  cachexia  and  hemoglobinuric  fever,  are  rarer  in 
the  negro. 

Instances  of  cachexia  followed  by  immunity  have  been  ob- 
served, especially  by  the  Itahan  school.  In  these  cases,  after 
recession  of  the  spleen  and  liver,  and  restoration  of  the  blood 
elements,  a  stable  immunity  resulted.  Subjects  of  existing 
cachexia,  even  though  free  from  clinic  evidences  of  acute  malaria 
for  years,  can  hardly  be  regarded  as  immune. 

Rarely  are  persons  encountered  in  highly  malarial  localities 
who  have  never  been  attacked  with  malaria.  Such  persons 
are  supposed  to  possess  congenital  immunity.  Celli''"*  obtained 
precise  histories  of  four  persons  living  in  the  Pontine  Marshes 
who  were  absolutely  immune,  having  never  had  malaria,  though 
they  took  no  prophylactic  precautions;  their  color  was  good,  and 
their  spleens  and  livers  normal.  In  persons  claiming  never  to 
have  had  malaria  allowances  must  be  made  for  the  possibility 
of  unrecognized  attacks,  especially  in  early  childhood,  which 
might  give  rise  to  an  acquired  immunity. 


36  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

In  conclusion,  the  resistance  of  the  black  race  to  malaria  is 
due  to  repeated  attacks  in  early  childhood,  and  not  to  any  great 
extent  to  heredity.  While  in  a  sense  natural  selection  is  a 
factor,  it  is  largely  an  individual  struggle,  the  selection  of  the 
fittest  occurring  in  infancy,  and  but  little  being  derived  from 
progenitors. 

Sex. — As  a  general  rule,  females  are  less  often  attacked  with 
malaria  than  males,  though  in  childhood  the  proportion  is  about 
even. 

That  women  are  less  frequently  infected  is  not  due  to  a  higher 
degree  of  resistance,  but  to  the  fact  that  they  are  less  often 
exposed  and  are  more  temperate  in  their  habits.  It  is  probable 
that  if  they  were  equally  exposed  with  males  they  would  be 
even  more  often  infected  than  the  latter,  on  account  of  the 
greater  delicacy  of  the  skin  and  the  manner  of  dress. 

In  certain  localities  women  are  not  less  frequently  attacked 
than  men.  In  Panama  there  is  said  to  be  very  little,  if  any, 
difference  between  the  sexes  in  this  respect.  In  the  Dutch 
East  Indies  European  women  are  more  susceptible  than  men. 
Davidson*""^  says  that  from  1871-75  the  death  rate  of  soldiers' 
wives  in  India  was  4.20  per  thousand,  as  compared  with  2.81 
for  the  men;  and  that  in  Bombay,  1885-86,  the  female  death 
rate  was  10.14;  that  of  males,  7.56. 

In  an  institution  in  Alabama,  Sims  and  Warwick*^"  found 
among  deaf  mutes  1.05  per  cent,  of  the  males  and  6  per  cent, 
of  the  females  infected;  among  blind,  6  per  cent,  of  the  males 
and  3  per  cent,  of  the  females. 

Pregnant  women  are  probably  less  often  infected  because, 
on  account  of  their  condition,  they  are  less  often  exposed ;  when 
exposed  they  are  very  susceptible.  The  puerperium  predis- 
poses to  malaria. 

Age. — Children  are  more  frequently  and  more  severely 
afflicted  with  malaria  than  adults.  This  is  probably  due  to  their 
more  dehcate  skin,  their  manner  of  dress,  sounder  and  more  pro- 
longed sleep,  and  inability  to  defend  themselves  against  mos- 
quito bites.  The  fact  that  cases  of  malaria  in  children  more 
often  escape  correct  diagnosis  may  account  somewhat  for  the 
greater  frequency,  especially  of  relapses. 


MALARIA  37 

The  subjoined  figures  show  the  distribution  of  malaria  accord- 
ing to  age: 


Age 

O-IO 

10-20 

20-30 

30-40 

40-so 

So-60 

60-70 

70-80 

80-90 

Thayer  and  Hewetson"' 

Rogers-^ 

x8 

2 
729 

146 

13 

499 

146 

204 
10 

398 
83 

69s 

130 

3 

230 

61 

424 

65 

36 

II 

3 

I 

144 
63 

100 

55 

Conti-"" 

Total 

994 

804 

272 

136 

66 

18 

4 

Endemic  Index. — The  percentage  of  children  infected  in  a 
given  locality  is  the  index  to  the  prevalence  of  malaria  in  that 
region.  As  Ross**-  expresses  it,  "There  is  probably  only  one 
really  accurate  method  by  which  we  can  determine  the  degree 
of  malaria  in  a  given  locality,  and  that  is  by  ascertaining  the 
average  time  in  which  a  newcomer  becomes  infected.  The 
shorter  this  period  the  greater,  evidently,  the  malaria  potential 
of  the  locality.  Native  children  constitute  the  class  of  new- 
comers most  accessible  for  making  the  estimate." 

The  most  accurate  method  of  determining  the  index  endem- 
icus  of  an  area  is  to  make  a  large  number  of  blood  examinations 
of  native  children  at  various  ages.  This  requires  a  great  deal  of 
time.  It  has  been  repeatedly  shown  that  in  regions  where 
malaria  prevails  extensively  a  large  per  cent,  of  young  children 
harbor  the  parasites  without  manifesting  any  symptoms  of  the 
disease,  the  index  decreasing  as  the  age  increases.  For  this 
reason  young  natives  with  latent  malaria  are  the  source  of  the 
greatest  danger  to  the  community. 

Endemic  indices  for  the  United  States  have  been  determined 
in  very  few  instances. 

Sims  and  Warwick^^"  examined  the  blood  of  610  apparently 
healthy  children  and  adults  in  Alabama  and  found  that  between 
8  and  9  per  cent,  were  infected  with  malaria. 

Surgeon  von  Ezdorf  of  the  United  States  Public  Health 
Service  examined  the  blood  of  a  number  of  persons  in  several 
Southern  States  with  the  following  results: 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


Number  examined 

Per  cent,  infected 

664 

802 

3613 

6S 

3-7 
6.6 

North  Carolina 

8.5 
12.3 

In  calculating  the  endemic  index  a  sufficiently  large  number 
of  persons  should  be  examined  in  order  to  eliminate  error.  It 
has  been  estimated  that  if  fifty  persons  be  examined  and  the 
blood  of  twenty-five  found  to  contain  parasites,  the  margin  of 
error  being  20  per  cent.,  the  index  would  not  be  50  per  cent,  but 
between  30  and  70  per  cent.  Furthermore,  while  a  high  index 
indicates  widespread  malaria,  an  index  of  zero  must  not  be 
construed  to  indicate  an  entire  absence  of  the  disease,  since 
experience  has  shown  that  it  may  exist  where  the  index,  esti- 
mated in  this  manner,  is  zero. 

In  comparing  the  indices  of  two  localities  the  figures  should 
be  taken  at  corresponding  seasons,  since  the  index  of  a  given 
locality  varies  according  to  season. 

The  prevalence  of  splenic  enlargement  has  been  employed 
to  calculate  the  extent  of  paludism,  this  method  requiring  much 
less  time  than  the  examination  of  the  blood. 

The  spleen  rate  and  the  endemic  index,  estimated  by  a 
microscopic  examination  of  the  blood,  do  not  usually  correspond 
even  approximately.  Stephens  and  Christophers"^'  have  pre- 
pared the  following  table  to  illustrate  the  relation  between  the 
spleen  rate  and  the  parasite  rate: 

Endemic  index 


Calcutta 

Jalpaiguri 

Bustee  children 
School  children. 
Babu  children. . 

Mainaguri 

Rungamutty 

Sam  Sing 

Kurseong  I 

Kurseong  II 


MALARIA  39 

These  investigators  draw  the  following  conclusions:  i.  A 
high  endemic  index  may  exist  without  any  appreciable  spleen 
rate  (Africa). 

2.  A  high  spleen  rate  may  exist  in  adults  without  a  cor- 
responding parasite  infection. 

3.  In  India  (Bengal)  among  children  a  high  spleen  rate  is  a 
fair  indication  of  the  parasite  infection. 

4.  The  spleen  rate,  unlike  the  parasite  rate,  increases  up  to  a 
certain  age  limit  and  may  be  considerable  when  the  parasite  rate 
is  nil. 

I  do  not  beheve  that  the  spleen  rate  would  disclose  the  true 
endemic  index  of  regions  in  the  Southern  States. 

Length  of  Residence. — In  highly  malarial  regions,  especially 
in  the  tropics,  newcomers  are  usually  infected  during  the  first 
year. 

In  the  Southern  States  the  period  before  infection  varies 
greatly  according  to  circumstances.  Newcomers  who  Kve 
in  hygienic  surroundings,  and  who  observe  ordinary  precautions, 
may  go  for  years  without  developing  the  disease.  On  the 
other  hand,  persons  coming  South  who  take  no  precaution,  and 
who  expose  themselves  carelessly,  are  liable  to  be  attacked  early. 
Thus  it  is  said  that  when  the  Beaumont  oil  fields  were  opened 
up  people  flocked  there  from  nearly  every  section  of  the  country, 
and  nearly  every  newcomer  was  struck  down  within  a  few  weeks 
with  malarial  fever  of  some  form. 

Residence,  even  prolonged,  in  a  malarial  locahty  does  not  con- 
fer absolute  immunity  to  malaria. 

Change  of  Residence. — The  effect  of  a  change  of  residence 
upon  the  immunity  in  the  negro  race  has  been  referred  to. 

It  is  a  common  observation  that  moving  to  another  locahty 
"brings  the  malaria  out  of  the  system."  This  malaria  is  usually 
latent — always  so,  of  course,  if  the  new  residence  is  in  a  non- 
malarial  region.  It  is  not  uncommon  for  persons  who  have 
never  had  recognizable  paroxysms  to  suffer  an  outbreak  upon 
leaving  the  endemic  region. 

Occupation. — This  is  a  factor  in  the  etiology  of  malaria 
in  two  respects :  first,  by  reason  of  certain  occupations  exposing 
the  person  to  the  bites  of  mosquitoes;  second,  by  reason  of  the 


40  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

exposure  and  exertion  attending  certain  occupations  awakening 
latent  malaria. 

Rural  avocations  more  commonly  expose  to  malaria  than 
urban.  Occupations  which  necessitate  residence  at  highly 
malarious  spots  are  especially  dangerous,  as  well  as  those  that 
require  being  out  of  doors  at  night. 

Overturning  the  soil,  as  in  gardening,  farming,  ditching,  rail- 
road, levee,  and  canal  construction,  predisposes  to  malarial 
infection.  Fishermen,  soldiers,  night-watchmen,  engineers, 
and  timber  workers  are  often  exposed. 

Rice  culture,  requiring  as  it  does  the  retention  of  water  from 
the  surface  of  the  ground,  is  not  an  unalloyed  boon  as  an  in- 
novation into  many  of  our  Southern  States.  The  dangers  to 
the  community  from  the  growth  of  rice  were  recognized  many 
decades  ago  near  Savannah  and  Charleston. 

Social  Condition.  Civilization. — Formerly  malaria  attacked 
all  classes.  Many  noted  persons  were  frequently  infected,  and 
James  I  and  Cromwell  died  of  the  disease.  Moats  and  lakes 
near  castles  and  country  estates  were  doubtless  to  blame. 

Now  malaria  is  chiefly  a  disease  of  the  poor  and  ignorant 
classes.  The  man  in  the  well-constructed  and  properly 
screened  residence  is  much  less  hable  to  become  infected  than 
the  one  in  the  loosely  built  and  unprotected  hut.  The  occupa- 
tions and  food  of  the  poorer  classes  are  also  factors  in  the 
greater  prevalence  among  them. 

Persons  living  in  cities  and  towns  are  much  less  apt  to  be 
exposed  to  infection  than  those  living  in  villages  and  in  the 
country.  Many  towns  and  cities  in  the  heart  of  malarial  areas 
are  relatively  free  from  the  disease.  Suburbs  are  more  highly 
malarious  than  the  more  densely  populated  sections,  for  the 
reason  that  the  mosquito  has  more  opportunity  to  breed  in 
the  former. 

Other  Factors. — There  are  certain  factors  of  the  utmost 
importance  in  the  etiology  of  malaria,  and  before  the  truth  was 
known  were  looked  upon  as  causing  the  disease.  These  are 
over-work,  fatigue,  exposure  to  sun,  rain,  and  cold,  excesses  in 
Bacchus  and  Venus,  psychic  emotions,  loss  of  sleep,  traumatism, 
surgical    intervention,    over-eating,    hunger,    thirst,    digestive 


MALARIA  41 

disorders,  menstruation,  parturition,  intercurrent  affections, 
and  the  administration  of  certain  medicaments. 

Watermelons,  muscadines,  cucumbers,  and  other  articles 
have  yet  the  reputation  in  parts  of  the  South  of  causing  chills. 

The  administration  of  tuberculin  and  of  potassium  iodide 
is  said  to  be  followed  not  infrequently  by  outbursts  of  malaria. 
It  is  obvious  that  the  influence  of  these  factors  is  upon  la- 
tent malaria,  or  the  parthenogenetic  cycle  of  the  parasite's  life 
history. 

Insufficient  and  improper  food  both  lower  the  resistance  to 
new  infections  and  kindle  latent  malaria  into  activity. 

While  the  major  portion  of  many  older  works  on  malaria  was 
devoted  to  the  role  of  drinking  water  in  the  contagion  of  malaria, 
it  is  now  known  that  it  is  of  minor  importance. 

In  regard  to  the  immunity  to  malaria  enjoyed  by  opium- 
eaters,  Russell'"'''  states  that  the  observations  of  several  sur- 
geons of  extensive  experience  in  opium-eating  regions  confirm 
th'e  popular  belief  that  the  opium-eater  in  the  early  stages  of 
the  habit,  while  as  yet  not  constitutionally  broken  by  its  long 
continuance,  does,  as  a  matter  of  fact,  enjoy  considerable  im- 
munity from  malarial  aft'ections.  This  writer  concludes  that 
this  power  of  opium  is  partially  responsible  for  its  prevalence 
in  some  of  the  eastern  countries.  Moore*^^  testifies  also  that 
opium-smokers  are  more  resistant  to  malaria. 

Epidemics. — Malaria,  known  as  an  endemic  disease,  occa- 
sionally prevails  so  intensely  as  to  acquire  the  dignity  of  an 
epidemic.  Becoming  more  frequent  and  fatal  in  its  native 
haunts,  it  may  spread  to  regions  ordinarily  immune,  and  may 
even  assume  the  extent  of  a  pandemic. 

The  first  pandemic  of  which  we  have  any  knowledge  occurred 
in  1557  to  1558,  and  is  said  to  have  overspread  all  of  Europe. 
The  next  appeared  from  1678  to  1682,  and  was  nearly  as  exten- 
sive as  the  former.  Similar  epidemics  arose  during  1718-1722, 
1748-1750,  1770-1772,  and  1779-1783.  During  the  past 
century  an  epidemic  occurred  from  1806  to  181 2,  and  one  from 
1823  to  1827  is  said  by  Hirsch  to  have  been  one  of  the  most 
extensive,  severe,  and  persistent  of  pandemics,  of  which  reports 
were  received  from  almost  all  parts  of  the  world.     Between 


42  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

1845  ^^'^  1849,  3-iid  1855  and  i860  malaria  assumed  epidemic 
form,  and  the  great  pandemic  of  1866  to  1872  marked  the  inva- 
sion of  Mauritius  and  Reunion,  where  malaria  was  previously 
unknown. 

What  may  be  called  house  epidemics  or  domestic  epidemics 
are  common  in  the  experience  of  many  observers. 

It  is  well  known  that  the  residents  of  certain  houses  suffer 
much  from  malaria,  and  that  certain  houses  are  seldom  free  from 
the  disease  during  the  malarial  season.  For  this  local  condi- 
tions are  responsible. 

I  have  more  than  once  seen  as  many  as  half  a  dozen  cases  in 
one  family  at  the  same  time,  and  in  many  famihes  every  mem- 
ber is  successively  attacked  during  the  season. 

Modes  of  Infection. — The  only  known  modes  of  transmission 
of  malaria  necessary  to  consider  are:  (i)  congenital;  (2)  arti- 
ficial inoculation;  and  (3)  inoculation  through  the  bites  of  cer- 
tain species  of  mosquitoes. 

Congenital  Malaria. — It  was  formerly  beheved  that  ma- 
laria was  not  infrequently  transferred  from  mother  to  fetus. 
Ducheck^-  pubUshed  a  case  in  1858  of  a  child  whose  mother 
suffered  from  malarial  paroxysms  during  pregnancy.  The 
child  djang  three  hours  after  birth,  at  autopsy  the  Hver  and 
spleen  were  found  to  be  enlarged,  and  the  spleen  and  blood  of 
the  portal  vein  contained  considerable  pigment. 

Two  cases  are  reported  by  Felkin.*^"  In  the  first  case 
the  diagnosis  was  based  upon  intrauterine  quivering  of  the  fetus, 
enlarged  spleen  at  birth,  and  fever  later,  the  date  of  which  is 
not  recorded.  In  the  second  case  the  mother  had  never  had 
malaria,  having  never  been  outside  Edinburgh,  but  the  infection 
is  attributed  to  the  father,  who  had  contracted  malaria  in 
Africa  several  years  previously  and,  as  Felkin  beHeves,  had  trans- 
mitted the  disease  to  no  less  than  three  infants. 

Watson''^^  cites  the  case  of  a  woman  who  was  suffering  with 
tertian  ague.  On  alternate  days  when  she  missed  the  paroxysms 
she  could  feel  the  child  shiver  with  chills.  Bark  was  prescribed 
and  the  paroxysms  of  the  fetus  were  first  interrupted,  then  those 
of  the  mother. 

However,  of  numerous  cases  recorded  by  a  score  or  more  of 


MALARIA  43 

early  writers,  all  are  open  to  two  objections:  First,  the  diagno- 
sis was  not  certainly  estabKshed;  secondly,  postnatal  infection 
was  not  excluded. 

Marchiafava  and  Bignami^^  mention  four  cases  in  which  the 
blood  of  the  fetuses  of  malarial  mothers  was  entirely  negative. 

Thayer"*^^  records  a  case  of  a  negress  who  had  had  malaria 
at  least  five  months  and  whose  blood  contained  three  groups  of 
the  quartan  parasites  when  she  gave  birth,  during  a  paroxysm, 
to  a  child  whose  blood,  upon  repeated  examination,  was  found 
free  from  parasites  and  pigments.  While  both  parasites  and 
pigment  were  found  upon  the  maternal  side  of  the  placenta, 
none  were  found  upon  the  fetal  side. 

Sereni,-'  who  examined  the  blood  of  four  infants  born  of 
malarial  mothers,  was  unable  to  find  evidences  of  malaria  in 
any  case. 

Ziemann,^^  likewise,  in  four  cases  of  new-born  children  of 
malarial  infected  mothers,  had  uniformly  negative  results. 

I  have  upon  several  occasions  obtained  blood  from  infants, 
immediately  after  birth,  whose  mothers  harbored  malarial 
parasites,  and  in  no  case  have  parasites  been  detected.  Similar 
results  have  been  obtained  by  Bastianelli,'^  Caccini,^^  Borne, ''^ 
Schoo,"  F.  Plehn,-'  Terburgh,^^  A.  Plehn,^^  Wellman,!!^  and 
others. 

Pezopoulos  and  Cardamatis,''^*  based  the  following  conclu- 
sions upon  six  cases,  five  full-termed  labors  and  one  abortion, 
which  they  studied. 

1.  In  the  blood  of  the  six  mothers  there  were  parasites,  more 
or  less  abundant. 

2.  In  the  blood  of  the  new-born  and  of  the  aborted  fetus, 
examined  a  few  hours  after  expulsion,  there  were  no  parasites. 

3-  In  the  blood  of  the  liver  and  spleen,  as  well  as  in  sections 
of  these  organs  of  the  two  fetuses  which  were  examined  post- 
mortem, no  parasites  were  found. 

4.  In  the  blood  taken  from  the  maternal  surface  of  the 
placentce  of  the  five  new-born  children  there  were  parasites  in 
abundance,  while  in  the  blood  taken  from  the  fetal  surface  there 
were  no  parasites,  or  at  most  a  very  few. 


44  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

5.  In  blood  taken  from  the  umbilical  cord  no  parasites  were 
found. 

6.  In  the  blood  of  the  placenta  of  the  aborted  fetus  no  para- 
sites could  be  detected. 

Bein  and  Kohlstock-^  are  said  to  have  found  malarial  para- 
sites in  the  blood  of  a  four-months-old  child  born  some  time 
after  the  arrival  of  the  mother  in  a  region  free  from  malaria. 

Winslow***  records  a  case  which  he  believes  to  be  congenital, 
though  the  parasites  were  not  detected  until  the  child  was 
eleven  weeks  old. 

A  case  of  malarial  fever  in  infancy  thought  to  be  maternal  in 
origin  is  reported  by  Peters.*^"  The  examination  of  the  blood 
on  the  second  and  third  days  after  birth  was  negative,  though 
parasites  were  found  on  the  fifty-first  day. 

Moffatf*^^  observed  a  case  supposed  to  be  congenital  malaria, 
though  the  parasites  were  not  detected  before  the  seventh 
week. 

Bouzian,"'^  in  Algeria,  detected  parasites  in  the  blood  of  an 
infant  only  twelve  days  old. 

Hitte^'^  collected  from  the  literature  twenty-one  cases  of 
malaria  considered  congenital.  In  thirteen  of  these  the  blood 
was  not  examined ;  in  one  parasites  were  detected  four  months 
after  birth,  and  in  five  parasites  were  found  from  several  weeks 
to  two  months  after  birth.  The  remaining  two  cases  were  ob- 
served by  Hitte  personally,  who  claims  to  have  found  parasites 
in  the  blood  obtained  from  the  umbilical  cords.  The  mothers 
of  both  children  were  suffering  with  malaria. 

Parasites  were  found  by  Simms  and  Warwick*^"  in  the  blood 
of  three  babies  between  three  and  seven  days  old;  the  mothers 
had  previously  had  malarial  paroxysms. 

Holt^^"*  mentions  a  case  in  which  he  states  there  seems  little 
doubt  that  the  disease  was  contracted  in  iitero.  The  mother 
had  been  suffering  with  tertian  intermittent.  Eighteen  hours 
after  birth  the  child  showed  evidences  of  a  malarial  paroxysm. 
The  next  day  malaria  organisms  were  found  in  the  blood. 

Ecocomous*^^  reports  six  cases  with  almost  conclusive  evi- 
dence of  congenital  origin.  In  each  of  these  cases  the  blood, 
examined  from  eight  to  forty-eight  hours  after  birth,  contained 


MALARIA  45 

malarial  parasites.  The  mothers  had,  previous  to  delivery, 
suffered  with  malaria. 

BeP''®  mentions  a  female  patient  who  died  of  pernicious 
malaria.  The  parasite  was  found  in  the  blood,  pericardium, 
meninges,  and  spleen,  as  well  as  in  a  seventh-month  fetus. 

As  may  be  inferred,  properly  proven  cases  of  congenital 
malaria  are  rare.  This  reluctance  of  the  parasites  to  pass 
through  the  placenta  is  in  keeping  with  their  aversion  to  leave 
the  blood-vessels.  It  has  been  pointed  out  that  no  parasites  are 
found  in  the  hemorrhages  and  perivascular  exudates  in  cases  of 
pernicious  malaria,  though  they  may  exist  in  hordes  within  the 
vessels.  Congenital  malaria  is  probably  to  be  explained  in  the 
majority  of  cases  through  placental  lesions  permitting  direct 
mingling  of  maternal  and  fetal  blood  during  parturition. 

Inoculation. — Even  before  the  parasite  of  malaria  was  dis- 
covered Gerhardf^^  succeeded,  employing  the  blood  of  malarial 
subjects,  in  inoculating  healthy  persons  with  malaria. 

Since  then  many  similar  experiments  have  been  performed. 
Tertian  malaria  has  been  transmitted  by  inoculation  by  Bein, 
Bacelli,  and  Celli  and  Santori;  estivo-autumnal  by  Gualdi  and 
Antolisei,  Di  Mattei,  Celli  and  Santori,  Bastianelli  and  Bignami, 
and  Elting. 

The  injection  of  blood  containing  only  crescents  gave  nega- 
tive results  in  the  experiments  of  Thayer,  Bastianelli,  Bignami, 
and  Elting.  Di  Mattei  and  Calandruccio,  however,  observed  an 
irregular  form  of  fever  to  follow  such  an  injection.  This  can  be 
explained  only  by  parthenogenesis. 

The  injection  of  blood  containing  certain  species  of  parasites 
is  followed  by  fever  characteristic  of  that  species,  and  these 
parasites  are  to  be  found  in  the  blood  of  the  person  inoculated. 

There  are  those  who  cannot  be  successfully  inoculated  with 
one  species  of  parasite  but  can  with  another.  It  has  been 
shown  also  that  one  species  of  parasite  often  disappears  from  the 
blood  upon  inoculation  with  a  different  species. 

The  degree  of  development  of  the  parasites  apparently  has  no 
effect  upon  the  result,  since  the  disease  develops  as  readily  after 
the  injection  of  blood  containing  adult  organisms  as  after  that 
containing  young  parasites.     It  is  immaterial  also  whether  the 


46  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

blood  be  injected  intravenously  or  subcutaneously.  A  very 
small  amount  of  blood,  even  less  than  one  drop,  is  often  suffi- 
cient for  inoculation. 

The  injection  of  defibrinated  blood,  of  centrifugalized  cor- 
puscles, and  of  blood  diluted  with  an  equal  quantity  of  distilled 
water  and  inoculated  immediately  have  given  positive  results. 
The  injection  of  dissolved  dried  blood,  and  blood  diluted  with 
an  equal  quantity  of  distilled  water  and  allowed  to  stand  an 
hour,  have  proven  negative. 

Jeffries"'^''  reports  the  case  of  a  New  York  surgeon  who  had 
never  had  malaria,  supposed  to  have  contracted  the  disease  by 
pricking  his  finger  several  times  during  an  operation  upon  a 
woman  infected  with  malaria.  .Sixteen  days  after  the  operation 
the  surgeon  had  the  first  chill  and  had  several  subsequently. 
The  blood  contained  many  estivo-autumnal  parasites. 

Efforts  to  inoculate  the  lower  animals  with  human  malaria 
have  been  fruitless.  Such  attempts  have  been  made  upon 
horses,  mules,  dogs,  monkeys,  rabbits,  mice,  guinea-pigs, 
hedgehogs,  bats,  wolves,  cats,  pigeons,  doves,  magpies,  screech- 
owls,  turtles,  frogs,  and  lizards. 

DISSEMINATION  OF  MALARIA.  BY  MOSQUITOES 

The  discovery  by  Ross  of  the  role  of  the  mosquito  in  the 
dissemination  of  malaria  is  the  most  startling  achievement  of 
modern  medical  science. 

Mosquitoes  do  not  cause  malaria;  they  carry  it  from  infected 
to  healthy  persons.  The  parasites,  sucked  with  blood  from  a 
malarial  individual,  undergo  a  cycle  of  development  within  the 
body  of  the  mosquito,  and  are  then  inoculated  into  healthy 
persons.  Man  is  merely  the  intermediate  host  of  the  parasite, 
the  mosquito  is  the  definitive  host,  and  it  has  been  said  that 
man  gives  malaria  to  the  mosquito,  and  not  the  mosquito  to 
man. 

Not  all  species  of  mosquitoes  can  serve  as  hosts  for  the  ma- 
laria parasite.  It  is  only  certain  members  of  the  subfamily  Ano- 
phelinas  that  have  been  found  to  act  in  this  capacity.  Of  this 
subfamily  the  following  have  been  determined,  with  more  or 
less  certainty,  to  be  malaria  carriers: 


47 


Anopheles  annulipes. 
Anopheles  bifurcatus. 
Anopheles  cohaesa. 
Anopheles  crucians. 
Anopheles  farauti. 
Anopheles  formosaensis . 
Anopheles  maculipennis. 
Anopheles  martini. 
Anopheles  pscudopunclipennis. 
Anopheles  pursali. 
A  nopheles  quadrimaculalus. 
Anopheles  larsimaculala. 
Anopheles  vincenli. 
Cellia  albimaniis. 
Cellia  argyrotarsus. 
Cellia  pharoensis. 
Cycloleppleron  grabhamii. 
Myzomyia  Christopher  si. 
Myzomia  culicifacies. 
Myzomyia  ftmesta. 
Myzomyia  Hispaniola. 
Myzomyia  Ludlowii. 


Myzomyia  Lutzii. 
Myzomyia  picla. 
Myzomyia  Rosii. 
Myzomyia  Turhhudi. 
Myzorhynckus  harbiroslris. 
Myzorhynchiis  Coustani. 
Myzorhynchus  fuliginosus. 
Myzorhynchiis  paliidis. 
Myzorhynchus  sinensis. 
Myzorhynchus  iimbrosus. 
Myzorhynchiis  Ziemanni. 
Nyssorhynchus  annulipes. 
Nyssorhynchus  Jamesii. 
Nyssorhynchus  maculalus. 
Nyssorhynchus  maculipalpis. 
Nyssorhynchus  Stephensii. 
Nyssorhynchus  Theobaldi. 
Nyssorhynchus  Willmori. 
Pyretophorus  Chaudoyei. 
Pyretophorus  costalis. 
Pyretophorus  jeyporensis. 
Pyretophorus  superpiclus. 


Not  all  of  these  mosquitoes  serve  equally  well  as  hosts  of  the 
malaria  parasites.  Myzomyia  Rosii  is  a  very  poor  carrier  of 
malaria,  while  the  Christophersi  is  a  very  efficient  carrier. 

As  yet  very  little  is  known  of  the  relation  between  the 
species  of  mosquitoes  and  species  of  malarial  parasites.  Pyre- 
tophorus costalis  is  known  to  transmit  tertian,  quartan,  and 
estivo-autumnal  malaria,  while  Myzorhynchus  sinesis  carries 
tertian  and  quartan,  but  not  estivo-autumnal  malaria. 

It  is  possible  that  some  mosquitoes  acquire  a  sort  of  immunity 
to  malaria  which  may  account  for  their  incompetence  as  malaria 
disseminators.  There  are  certain  regions  where,  in  spite  of 
members  of  a  malaria-bearing  species  of  mosquito  and  the  immi- 
gration of  infected  persons,  malaria  does  not  spread,  though 
temperature  and  other  conditions  are  apparently  favorable. 

The  food  of  mosquitoes  has  much  to  do  with  their  suscepti- 
bility to  infection.  Experiments  have  shown  that  Anopheles 
maculipennis  fed  upon  fruits  and  sweets  are  not  readily  infected 
from  feeding  upon  malarial  blood,  but  if  allowed  only  water  for 
several  days  before  and  after  feeding  on  malarial  blood  they 
are  almost  always  infected. 


40  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

One  feeding  upon  blood  containing  parasites  does  not  always 
sufSce  to  infect  the  mosquito.  Daniels,^^*  investigating  this 
subject,  examined  57  mosquitoes  which  had  fed  once  or  oftener 
at  intervals  of  two  days. 

Per  cent. 

Nineteen  fed  only  once,  and  five  had  zygotes 26.0 

Thirteen  fed  twice,  and  six  had  z3'gotes 46 .  o 

Sixteen  fed  three  times,  and  ten  had  zygotes 62.0 

Nine  fed  four  times,  and  six  had  zygotes 66 . 6 

Of  these  57  anopheles  27,  or  47.5  per  cent.,  were  infected. 

The  effect  of  fertilization  upon  the  power  of  mosquitoes  to 
transmit  malaria  is  not  definitely  settled,  but  it  is  thought 
by  some  that  fertilized  females  are  the  most  desirable,  if  not 
indeed  the  sole,  hosts  of  the  parasite. 

In  order  that  anopheline  mosquitoes  may  be  infected  from 
malarial  blood  it  is  necessary  that  the  sexual  forms  of  the  para- 
site be  present  in  sufhcient  numbers,  of  proper  maturity,  and 
suitable  proportion  of  sexes. 

How  is  the  existence  of  the  malaria  parasite  perpetuated? 
Why  does  not  the  disease  become  extinct  over  winter  when 
there  are  apparently  no  mosquitoes  to  further  the  life  history 
of  the  organism  ? 

The  subject  of  latent  or  chronic  malaria  furnishes  the  solu- 
tion. The  parasites  here  lie  dormant  or  undergo  parthenogene- 
sis at  longer  or  shorter  intervals,  and  are  ready  the  following 
season  for  the  sexual  cycle  in  the  body  of  the  definitive  host,  the 
mosquito. 

It  is  possible  that  in  a  few  instances  the  parasites  persist  in 
the  bodies  of  hibernating  mosquitoes.  While  some  investi- 
gations have  led  to  a  different  conclusion,  Martirano  has  found 
in  the  neighborhood  of  Rome  as  late  as  the  middle  of  March 
that  from  i  to  5  per  cent,  of  anophehnes  were  infected,  and 
Stephens  and  Christophers  observed  at  Freetown,  during  the 
dry  season,  that  from  5  to  20  per  cent,  were  infected.*^ 

From  analogy  with  the  transference  of  Texas  fever  hematozoa 
by  the  tick  to  its  progeny,  it  has  been  sought  to  establish  such 
an  inheritance  of  malaria  parasites  by  mosquitoes,  but  it  must 
be  considered  as  yet  unproven  that  infected  mosquitoes  can 
communicate  the  infection  to  their  offspring. 


MALARIA  49 

The  relation  of  the  mosquito  to  malaria  explains  the  preva- 
lence of  the  latter  with  reference  to  season,  temperature,  and 
rainfall.  It  explains  malaria  as  a  disease  chiefly  of  low  altitudes 
and  marshy  regions;  a  disease  of  the  country  rather  than  of  the 
city.  House  epidemics  of  malaria  are  thus  rendered  clear  and 
the  relation  of  ship  malaria  and  proximity  to  the  shore  become 
obvious.  The  bearing  of  age,  sex,  and  occupation  upon  the 
endemic  is  in  thorough  harmony  with  the  theory.  That  malaria 
is  more  easily  contracted  at  night  is  understood  from  the  feed- 
ing habits  of  the  malarial  mosquitoes.  That  all  measures  di- 
rected toward  the  prevention  of  mosquito  bites  are  followed  by  a 
commensurate  reduction  of  the  prevalence  of  malaria  is  one  of 
the  strongest  arguments.  The  analogy  with  filiariasis,  Texas 
fever,  hematozoan  infection  of  birds,  and  similar  diseases 
strengthens  the  theory.  Numerous  and  accurate  experiments 
have  absolutely  proven  the  dissemination  of  malaria  by  certain 
mosquitoes. 

The  sexual  cycle  of  the  parasite  within  the  mosquito  has  been 
followed  many  times. 

An  objection  that  has  been  frequently  urged  against  the 
"mosquito  theory"  is  that  there  are  numerous  locahties  in  which 
mosquitoes  abound  and  from  which  malaria  is  entirely  absent; 
indeed,  mosquitoes  are  said  to  be  well  nigh  intolerable  in  portions 
of  the  arctic  regions.  It  must  be  remembered,  however,  that 
only  a  certain  subfamily  of  mosquitoes  can  serve  as  hosts  for  the 
parasite.  Furthermore,  the  surrounding  temperature  must  be 
suitable  for  the  sexual  development  of  the  parasite  within  the 
definitive  host. 

It  was  formerly  maintained  that  there  were  highly  malarial 
regions  in  which  there  were  no  mosquitoes,  and  a  number  of  such 
places  have  been  reported.  But  in  each  case  where  investi- 
gated by  a  competent  observer  anopheline  mosquitoes  are  such 
that  they  may  be  easily  overlooked  except  by  an  expert.  Re- 
tiring to  dark  recesses  during  the  day,  biting  only  at  night,  and 
not  singing  a  great  deal,  their  presence  may  not  be  felt,  espe- 
cially by  persons  in  whom  the  bites  do  not  cause  much  irritation. 

It  may  therefore  be  stated  confidently  that  there  is  no  endemic 
malaria  without  mosquitoes. 
4 


50  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

The  misproportion  between  the  number  of  infected  anophe- 
lines  and  the  number  of  cases  of  malaria  has  been  cited  to  over- 
throw the  mosquito  doctrine.  In  Algiers  Sergenf"^  found  4  per 
cent,  of  the  anopheles  and  100  per  cent,  of  the  children  infected. 
A.  Plehn*^  found  in  one  of  the  most  malarial  localities,  Cam- 
eroon, among  860  anopheles,  only  2.2  per  cent,  infected. 
Stephens  and  Christophers*'^  believe  that  about  5  per  cent,  of 
all  the  anopheles  of  tropic  Africa  are  infected.  At  Aro  they 
found  the  sporozoit  rate  in  anopheles  caught  in  native  huts  to  be 
50  per  cent. 

It  should  be  borne  in  mind  that  one  infected  anopheline 
mosquito  is  capable  of  infecting  a  number  of  persons.  Also  the 
sporozoit  rate  varies  according  to  season  and  according  to  the 
kind  of  mosquito,  since  it  has  been  shown  that  some  species  are 
better  malaria  carriers  than  others. 

Finally,  it  has  been  maintained  that  persons  who  have  never 
had  malaria  have  contracted  it  in  uninhabited  wildernesses, 
where,  obviously,  only  uninfected  anophehnes  would  be  found, 
since  man  is  the  only  intermediate  host  of  the  parasite. 

To  this  may  be  answered  that  no  such  instance  has  been  so 
accurately  reported  as  to  prove  conclusively  that  infection  has 
ever  occurred  under  these  circumstances. 

THE  MALARIA-BEARING  MOSQUITOES 

The  genus  Anopheles  was  estabHshed  in  1818  by  Johann 
Meigen.  The  bestowal  of  the  name  appears  prescient,  since 
anopheles  signifies  troublesome  or  hurtful. 

Of  the  fifty  or  more  species  and  subspecies  of  anophelines 
now  known  eight  occur  in  the  United  States:  A.  maculipennis, 
A .  punctipennis,  A .  crucians,  A .  franciscanus,  A .  pseudopuncti- 
pennis,  A .  barberi,  C.  argyrotarsus,  and  C.  albipes. 

Breeding  Places. — The  different  species  of  anophelines  vary  a 
great  deal  in  the  choice  of  a  breeding  place.  Furthermore,  with 
each  species  there  may  be  said  to  be  places  of  choice  and  places 
of  necessity. 

Contrary  to  the  usual  custom  of  culex,  the  anopheles  usually 
selects  water  more  or  less  pure  in  which  to  deposit  her  ova. 


MALARIA  51 

Ground-water  appearing  at  the  surface  is  especially  suitable. 
Pools  of  at  least  some  degree  of  permanence  are  preferred  to 
those  which  might  dry  before  the  aquatic  stage  of  the  insect  is 
completed.  Natural  accumulations  of  water  more  often  con- 
tain anopheles  larvae  than  do  artificial  collections.  Pools,  ponds, 
swamps,  inlets  of  lakes,  and  of  small,  slowly  flowing  streams, 
ditches  along  roadsides,  canals,  borrow  pits  along  railroads  and 
levees,  and  rice  fields  are  common  breeding  places.  Water 
contained  in  the  tracks  of  animals  may  harbor  larvce. 

When  water  is  scarce,  as  during  the  dry  season,  anopheline 
larvae  may  be  found  in  tubs,  barrels,  buckets,  bottles,  cisterns, 
mollusc  and  cocoanut  shells,  in  water  retained  by  the  leaves 
and  stalks  of  tropic  plants,  or  even  within  vases  in  dwellings, 
though  these  locations  are  to  be  regarded  as  places  of  necessity 
and  not  of  choice. 

In  regard  to  salt  water  as  a  medium  for  anopheline  larvae 
many  opinions  are  held.  It  seems  that  the  species  indigenous  to 
the  United  States  do  not  breed  in  salt  water,  and  this  was  the 
experience  of  Celli  and  other  Italian  investigators.  However, 
Centanni  and  Orta^*"  found  anopheles  larvae  in  water  containing 
8.77  per  1,000  of  sodium  chloride.  Ficalbi  and  others'*^"  found 
them  in  water  containing  40  to  50  grams  of  sodium  chloride  per 
liter.  In  Algiers  and  the  Dutch  Indies  anophelines  are  found 
breeding  in  concentrated  sea-water,  and  Banks"^  found  M. 
Ludlowii  breeding  in  sea-water  in  the  Philippines.  Bancroft  in 
Queensland  found  a  species  of  anopheles  breeding  in  sea-water, 
and  at  Accra,  on  the  west  coast  of  Africa,  Stephens  and  Chris- 
tophers''^^ obtained  numerous  anopheline  larvae  from  water 
containing  6  per  cent,  of  salt.  De  VogeP^^  at  Semarang  found 
certain  kinds  of  anopheles  breeding  not  only  in  sea-water,  but  in 
that  which  had  been  condensed  to  half  its  volume. 

Ova  of  Anophelines. — These  mosquitoes  do  not  deposit  their 
eggs  in  a  raft-hke  mass,  as  do  the  culex.  They  are  laid  in  irregu- 
lar piles,  but  soon  become  scattered,  he  horizontally,  and  may 
form  attractive  patterns  upon  the  surface  of  the  water.  In 
captivity  the  eggs  may  be  laid  upon    some  floating    object. 

The  ova  are  from  0.7  to  i.omm.  in  length  by  about  0.16  mm. 
in  breadth.     They  are  fusiform  in  shape  and  somewhat  broader 


52 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


at  one  end  than  at  the  other.  The  lower  surface  is  convex,  the 
upper  nearly  flat.  From  the  middle  third  of  each  side  protrudes 
a  transversely  corrugated  membrane  which  acts  as  a  float,  some- 


-A  raft  of  culex  ova. 


what  after  the  manner  of  the  air  chambers  of  a  lifeboat.  Around 
the  margin  of  the  upper  surface  of  the  ovum  is  a  frill,  usually 
transversely  corrugated.     When  first  laid  the  eggs  are  whitish, 


Fig.  2. — Patterns  assumed  by  anooheles  ova. 


Fig.  3. — Anopheles  ova. 


but  soon  become  almost  black.  The  head  of  the  larva  lies  in 
the  broad  end  of  the  egg  and  escapes  by  loosening  a  circular  cap 
from  this  end.  It  is  said  that  if  an  ovum  is  partially  removed 
from  the  water  the  broad  end  always  hangs  downward  in  order 


Fig.  4. — A  young  anopheles  larva.     Magnified. 

that  the  larvae  may  be  born  into  the  water  instead  of  into  the 
air.    , 

The  duration  of  the  egg  stage  varies  with  the  temperature, 
but  is  generally  from  two  to  four  days. 

Stephens  and  Christophers^-"  did  not  succeed  in  hatching  the 


56 


Fig.   5. — Half-giown  anopheles  larva,     ilagnified. 


Fig.  6. — Full-grown  anopheles  laiva. 


Fig.  7. — Anopheles  pupa.     Magnified. 


54  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

ova  after  desiccation  for  two  or  three  days,  but  Grassi''*"  is  said 
to  have  hatched  them  after  keeping  them  dry  for  twelve  days. 
The  Larva. — The  head  of  the  anopheles  larva  is  more  or  less 
globular;  the  eyes  are  situated  laterally  at  the  broadest  part  of 
the  head.  The  antennas  are  rod-shaped  and  unjointed;  at  the 
end  are  two  leaflets,  between  which  arises  a  branched  hair. 
The  mouth  parts  consist  of  the  feeding  brushes  or  whorl-organs, 


-■^^^ate; 


Fig.  8. — Head  of  anopheles.     Magnified. 

the  maxillary  palps,  the  mandibles,  the  under  lip,  and  the 
clypeus. 

The  neck  is  very  narrow  in  the  full-grown  larva. 

In  the  young  larva  the  thorax  is  little,  if  any,  wider  than  the 
head,  but  in  older  specimens  it  is  much  wider. 

There  are  nine  post- thoracic  segments.  The  first  three  seg- 
ments bear  branched  lateral  hairs.  The  third  to  the  seventh 
segments  have  upon  the  dorsum  a  pair  of  fan-shaped  structures, 
known  as  the  palmate  hairs. 

The  eighth  segment  contains  the  two  openings  of  the  respira- 
tory system,  which  ends  abruptly  at  the  dorsum  of  this  segment 


MALARIA  55 

without  the  prolonged  breathing  tube  of  the  other  subfamihes. 
The  ninth  or  caudal  segment  bears  four  flaps  containing  re- 
spiratory  branchiae.     This  segment  is  armed  with  two  large 
tufts  of  hair 


Fig.  g. — Tail  of  anopheles  larva.     Magnified. 

The  color  of  the  larva  varies  greatly,  according  to  food  and 
environment,  and  may  be  grayish,  green,  almost  black,  reddish, 
or  mottled  with  black  or  white. 

The  full-grown  larva  is  about  8  mm.  in  length. 

Anophehne  larvae  are  omnivorous.     Their  diet  consists  of  the 
spores  of  alga,  diatoms,  animalcules,  bacilli, 
other  larvae,  moulted  skins,  mosquitoes,  and 
other  small  insects.      In  captivity  they  eat 
dry  rice  greedily. 

The  customary  location  of  these  larvae  is 
at  the  surface  of  the  water  near  the  edge  of 
the  pool  where  they  may  remain  almost  mo- 
tionless for  long  periods.  The  characteristic  position  is  par- 
allel with  the  surface  of  the  water  and  so  close  to  it  that  a 
portion  of  the  dorsum  appears  to  rise  above  the  surface,  which. 


Fig.  lo. — A  pal- 
mate hair. 


56 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


however,  is  not  the  case.  When  feeding,  the  constant  motion 
of  the  mouth  parts  creates  a  flow  of  water  toward  the  mouth, 
bringing  in  small  particles  of  food.  The  head  is  often  rotated 
suddenly,  so  that  it  turns  through  an  arc  of  i8o  degrees  the  lower 


II. — Adult  culex  larva. 


surface  looking  uppermost.  On  taking  hold  of  something  too 
large  to  swallow  the  larva  will  often  shake  the  head  vigorously 
and  may  bend  the  body  to  steady  the  particles  against  the  last 
segments  of  the  body.  In  captivity  they  often  rest  with  the  tail 
against  the  sides  of  the  container  and  the  head  toward  the  center, 
when  numerous  forming  a  fringe  around  the  circumference. 
Locomotion  is  very  jerky  and  irregular.     When  disturbed  they 


Fig.  12. — Resting  positions  of  laivae:  c,  Culex;  b,  anopheles. 

not  infrequently  feign  death.  From  the  behavior  of  the  ano- 
pheline  larvae  it  does  not  appear  that  the  sense  of  sight  is  very 
acute. 

Culex  larvae  have  been  thawed  out  of  ice  in  which  they  were 
imbedded  and  have  proceeded  to  develop  into  insects,  but 


MALARIA  57 

SO  far  as  I  am  aware  this  has  not  been  done  with  anopheles. 
The  latter  have,  however,  been  found  in  water  under  a  frozen 


Fig.    13. — Male  ano|ihfles. 


Fig.   14. — Female  anopheles. 

surface.     They  may  exist  for  a  few  hours  to  a  few  days  upon 
moist  mud. 

The  duration  of  the  larval  stage  varies  according  to  tem- 


50  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

perature,  food,  and  possibly  other  conditions.  The  limits  may 
be  placed  at  from  ten  to  twenty-six  days.  In  warm  climates 
when  suitable  food  is  abundant  the  duration  is  ordinarily  twelve 
or  fourteen  days.  In  cooler  climates  and  seasons  the  duration 
is  longer. 

Anopheles  and  culex  larvae  may  be  differentiated  by  the  fol- 
lowing gross  characteristics: 

Anopheles  Culex 

Habitually  at  the  surface  of  the  water.  At  the  surface  to  breathe  only. 

Position  parallel  with  the  surface.  Jiangs  at  an  angle  of  50  to  60  degrees 

to  the  surface. 

No  respiratory  tube.  Large  respiratory  tube. 

In  full-grown  larvfe  the  head  is  smaller  Relatively  larger  head, 
than  the  thorax. 

The  Pupa. — While  the  larva  bears  some  resemblance  to  the 
imago,  the  pupa  resembles  neither.  It  has  been  compared  in 
shape  to  a  hypertrophied  comma.  The  anopheles  resembles 
culex  more  closely  in  this  stage  than  in  any  other.  The  head 
and  thorax  are  enclosed  together  in  a  semitransparent  shell, 
through  which  portions  of  the  mouth  parts,  wings,  and  legs 
may  be  detected.  Respiration  is  no  longer  transacted  through 
the  eighth  abdominal  segment,  as  in  the  larva,  but  through  the 
trumpet-shaped  spiracles  or  syphons  of  the  thorax.  This  ne- 
cessitates a  change  in  position,  the  abdomen  hanging  or  rather 
curved  around  the  cephalo-thoracic  segment.  The  eighth 
abdominal  segment  bears  a  pair  of  broad  paddles  for  locomotion. 
The  young  pupa  is  rather  light  in  color, 
but  rapidly  becomes  darker. 

The  pupce  are  more  easily  alarmed  than 
the  larvae,  and  when  disturbed  dart  wildly 
■j^      downward    with    rapid    jerks.       Being    of 
p;     J   Breathing    lower  specific  gravity  than  the  water,  they 

syphons  of  (a)  anoph-  rise  quickly  without  effort.  They  do  not 
ales  and  (6)  culex  pupae. 

eat. 

Italian  investigators'*^"  observed  that  the  nymphae  of  some 
mosquitoes  resisted  freezing  and  desiccation  to  a  remarkable 
degree.  Enclosed  for  several  hours  in  ice  they  were  yet  able 
to  develop,  and  kept  in  dry  soil  for  two  or  three  days  they  de- 
veloped when  placed  in  water. 


MALARIA 


59 


The  duration  of  the  pupal  stage  is  ordinarily  from  two  to  five 
days. 

The  following  points  may  serve  to  distinguish  anopheles  and 
culex  pupse: 

Anopheles  Culex 

Position  in  water  more  horizontal.  Position  more  vertical. 

Syphons  short,  square  truncated  ends,  Syphons    long    and    narrow,    slit-like 

attached  to  middle  of  thorax.  opening,  attached  to  posterior  part 

of  thorax. 

Longer     anteroposteriorly,     narrower  Shorter  and  broader, 
laterally. 

0 


a-  lb 

Fig.   i6. — Heads  of  {a)  cule.x  and  {h)  anopheles  females. 

When  approaching  the  emergence  of  the  imago  the  pupa 
■  becomes  motionless  at  the  surface  of  the  water;  the  abdomen  is 
extended  parallel  with  the  surface;  minute  air  bubbles  are  seen 
under  the  membrane,  which  then  splits  along  the  dorsal  line  of 
the  thorax.  The  imago  emerges  head  first,  then  the  thorax  and 
wings,  then  the  legs.  At  this  stage  the  insect  is  very  liable  to 
be  drowned  by  a  breeze  or  by  a  ripple  in  the  water. 

The  Imago. — Anopheles  is  distinguished  from  the  culex 
especially  by  the  palpi,  which  in  the  former  are  in  both  sexes 
almost  as  long  as  the  proboscis,  in  the  latter  the  palpi  of  the 
female  being  very  short.  Anopheles  is  more  slender,  the  head  is 
smaller,  and  the  legs  more  delicate.  The  palpi  of  the  female, 
being  thickly  scaled  and  lying  close  to  the  proboscis,  give  the 
impression  of  a  thick  beak,  which  contrasts  strongly  with  the 
short  palpi  and  slender  proboscis  of  the  culex.  The  wings  of 
the  anopheles  are  speckled,  which  is  not  the  case  with  any  of  the 
common  species  of  culex. 

The   sitting   of   anopheles  is   characteristic.     The   body   of 


6o  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

the  insect  is  at  an  angle  with  the  surface  upon  which  it  rests, 
the  proboscis  pointing  toward  the  surface,  sometimes  even 
touching  it.  This  angle  varies  in  different  anopheline  species, 
in  some  being  almost  a  right  angle,  when  the  insect  appears 
almost  Kke  standing  upon  its  head.  The  proboscis,  head,  thorax 
and  abdomen  are  in  the  same  Kne.  The  mosquito  at  rest  has 
been  compared  to  a  brad-awl  stuck  into  the  wall.  It  often 
rests  upon  the  first  two  pairs  of  legs,  waving  the  last  pair  in  the 
air.  Culex  at  rest  is  angular  and  humpbacked.  Stegomyia 
may  be  recognized  by  its  smooth,  velvety  coat  of  jet  black  and 


a-  \f 

Fig.  17. — Resting  positions  of  (a)  anopheles  and  (J)  cule.x. 

silvery  white,  the  banded  legs  and  abdomen,  and  the  lyre- 
shaped  ornamentation  of  the  thorax. 

The  principal  malaria  carriers  of  the  United  States  are  thus 
described  by  Giles:''*"' 

Anopheles  Macixlipemiis  (Meigen). — "Wings  with  four 
tufted  spots  on  the  wing-field,  the  costa  being  uniformly  dark 
except  at  the  apex,  where  its  color  fades  to  form  a  fairly  distinct 
spot;  tarsi  unhanded,  but  with  an  apical  yellowish  spot  I0  the 
first  joints.  Thorax  with  four  broad  ferruginous  stripes  formed 
of  golden  hairs,  between  which  the  darker  ground  color  is  left 
bare,  with  a  tuft  of  large  golden  scales  on  the  anterior  border. 
Abdominal  segments  brown  with  yellowish  basal  markings; 
anterior  femora  not  thickened  at  the  base. 

"Female. — Head  with  two  patches  of  creamy  scales  divided  by 
a  central  Kne,  the  rest  of  the  head  with  black  scales,  a  small  tuft 
of  white  hairs  in  front;  borders  of  the  eyes  white;  eyes  deep 
purplish  black;  antennee  dark  brown  with  pale  bands  and  with 
ferruginous  basal  joint,  pale  pubescence,  and  brown  hairs; 
proboscis  brown;  palpi  yellowish  brown  with  dense,  dark  scales 
at  the  base,  which  is  swollen,  shorter  than  the  proboscis.     Legs 


MALARIA  6 1 

with  pale  coxae;  femora  and  tibiae  yellowish  brown  below,  cov- 
ered with  dark  brown  scales  above;  knee  spot  yellow,  apex  of 
the  tibise  paler;  tarsi  slightly  darker  than  the  rest  of  the  leg. 

"Male. — Antennas  banded,  plume  hairs  brown,  last  joint 
darker;  proboscis  black  to  dark  brown;  palpi  dark  brown;  the 
last  two  joints,  which  are  clubbed,  have  a  number  of  short 
golden  hairs  internally  and  are  yellow  in  color,  clothed  with 
thick  black  scales,  through  which  the  yellow  underground  shows; 
the  last  joint  is  truncated.  Length  4  to  7.5  mm.,  male,  to  8  or 
10  mm.,  female.  This  species  varies  greatly  in  size,  the  wings 
shown  me  in  Italy  by  Professor  Grassi  being  quite  small,  while 
some  Canadian  specimens  in  the  British  Museum  are  huge 
gnats,  and  to  illustrate  this  I  have  superposed  on  the  plate  the 
drawing  of  one  of  Grassi's  specimens  on  the  outline  of  a 
Canadian  specimen." 

Anopheles  Crucians  (Wied). — "  Wings  with  white  spots  here 
and  there  on  the  brown  veins,  uniform  along  the  costa;  tarsi 
unhanded,  dusky  brown;  abdomen  uniformly  brown  with  gray 
hairs.     Thorax  red  brown  with  linear  markings." 

Description  from  Wied,  A.  Z.  I.,  page  12:  "Tawney;  the 
thorax  with  three  deeper- tinted  lines ;  the  abdomen  covered  with 
gray  hairs;  the  wings  with  dusky  spots  and  costa.  Length  sj^^ 
lines  (German)." 

"Coquillett,  in  his  recent  synoptic  table  of  North  American 
Culicidae,  states  that  'the  scales  of  the  last  veins  are  white, 
marked  with  three  black  spots;  palpi  with  white  at  the  bases  of 
the  last  four  joints,'  and  without  any  spot  on  the  costa,  as  seen 
in  A.  punctipennis. 

"Professor  Nuttall  sent  Mr.  Theobald  two  females  from 
America  in  spirit,  which,  although  much  damaged,  show  the 
two  features  mentioned  by  Coquillett  very  clearly,  readily 
distinguishing  the  species  from  the  C.  punctipennis  of  Say." 

The  hatching  of  the  first  brood  of  anophehnes  bears  an 
intimate  relation  to  the  seasonal  occurrences  of  malaria.  The 
seasonal  variations  of  different  species  are  probably  dependent 
upon  the  presence  or  absence  of  breeding  pools  suitable  to  par- 
ticular species.  Temperature  also  exerts  an  influence,  the 
hibernating  females  of  some  species  leaving  winter  quarters 


62  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

earlier  than  others,  and  hibernating  larvae  mature  at  different 
temperatures. 

While  the  anophelines  are  mosquitoes  of  low  altitudes,  they 
may  be  found  at  considerable  elevations.  Thus  in  the  Alps 
they  are  found  at  an  altitude  of  1,145  meters;  in  the  Apennines 
at  1,283  nieters;  in  Java  at  1,000  meters;  at  Harrar  at  2,000 
meters;  in  Africa  at  1,900  meters,  and  in  the  high  plateaus  of 
Mexico  at  2,000  meters. ^^^ 

It  is  the  rule  among  mosquitoes  that  only  the  females  are 
blood  suckers,  hence  it  is  this  sex  alone  that  is  concerned  in  the 


Fig.   18. — .\  female  mosquito  in  tlie  act  of  biting. 

propagation  of  malaria.  The  female  insect  sucks  not  only  the 
blood  of  man,  but  of  other  mammals,  birds,  occasionally  of  cold- 
blooded animals,  and  even  other  insects. 

There  are  a  few  exceptions  to  the  rule  that  males  do  not  bite. 
While  males  do  not  infrequently  Hght  upon  the  skin  and  probe 
around  with  the  proboscis,  they  usually  fly  away  without  par- 
taking of  any  blood.  The  habitual  diet  of  male  mosquitoes  is 
vegetarian.  They  are  very  fond  of  fruits,  as  bananas,  dates, 
pears,  apples,  melons,  and  of  the  nectar  of  flowers,  wine  and 
beer. 

Anopheline  mosquitoes  rarely  suck  blood  except  during  the 
night.  After  feeding  they  usually  retire  to  remote  and  dark 
corners  or  to  breeding  places  to  oviposit.  During  the  day  their 
reserved  habits  make  them  difficult  of  detection. 

A  point  of  great  practical  interest  is  the  length  of  ilight  of 
the  mosquito  and  the  extent  to  which  it  may  be  borne  by  the 
wind.  It  is  a  general  rule  that  mosquitoes  do  not  migrate  far 
from  their  native  pools  or  from  dwellings  where  nourishment 
may  be  obtained. 

It  is  very  unusual  for  anophelines  to  fly  farther  than  a  few 


MALARIA  63 

hundred  yards,  and  half  a  mile  may  be  regarded  as  the  maximum 
limit  of  flight.  They  are  poorer  flyers  than  most  other  species. 
For  this  reason  they  are  less  often  borne  by  the  wind,  since  they 
seek  shelter  when  a  breeze  arises.  While  the  wind  is  not  so 
generally  a  vehicle  for  the  dissemination  of  mosquitoes  as  com- 
monly beheved,  certain  species,  especially  of  salt-water  breeders, 
are  borne  by  the  wind  for  several  miles. 

The  preference  of  anophelines  for  certain  colors  has  been 


Fig.  ig. — Midgut  and  Malpighian  tubules  of  anopheles. 

demonstrated  by  GalH-Valerio  and  De  Jongh^*"  who  counted 
119  anopheHnes  resting  upon  dark  colors  and  ^^  upon  bright 
colors,  and  349  culex  upon  dark  colors  and  120  upon  bright. 

Mosquitoes  are  fond  of  the  odor  of  leather  and  are  usually 
plentiful  upon  harness  hanging  in  stables.  They  are  said  to 
prefer  the  odor  of  the  negro  to  that  of  the  white  man. 

Anophelines,  hke  other  malefactors,  prefer  darkness  rather 
than  light,  and  seek  the  sequestered  nooks  during  the  day. 

A  meal  of  blood  is  a  prerequisite  to  fertilization.  Females 
confined  with  males,  then  isolated  and  fed,  do  not  deposit  fer- 
tile eggs,  but  must  be  fed  first.  A  single  fertilization  is  sufficient 
for  several  batches  of  eggs.  These  are  usually  deposited  be- 
tween dusk  and  dawn.  Still  water  is  necessary,  since  the  female 
may  be  drowned  if  the  surface  is  agitated.     The  female  sits  upon 


64  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

the  water  or  upon  the  edge  of  floating  leaves  or  debris.  The  ova 
of  anopheHnes  are  deposited  upon  the  water  in  clumps,  but  soon 
separate  and  He  horizontally.  A  batch  of  ova  usually  numbers 
from  100  to  150.  Pressat**^  has  calculated,  on  a  basis  of  150 
ova  for  each  female,  hatching  50  per  cent,  females,  that  a  single 
female  in  one  season  produces  about  5,000,000,000  mosquitoes. 

It  is  impossible  to  determine  the  length  of  life  of  mosquitoes 
in  nature,  though  even  in  captivity  they  have  been  kept  for 
weeks.  AnopheHnes  have  been  kept  alive  five  days  without 
food  or  water,  and  for  about  two  months  fed  upon  bananas. 
The  males  are  not  so  long  lived  as  the  females. 

Stephens  and  Christophers^-"  say  there  is  evidence  that  the 
ova  can  survive  for  some  months  in  moist  earth  and  exposed  to 
frost.  Eysell*^''  and  GalH-VaJerio  and  De  Jongh"**"  state  that 
the  ova  of  most  species  of  mosquitoes  of  the  northern  temperate 
and  frigid  zones  may  hibernate. 

Mosquitoes  hibernate  in  the  larval  stage  also.  STnith^*" 
found,  in  New  Jersey,  larvae  of  culex  pungens  in  ice  contained  in 
pitcher  plants,  and  beHeves  that  larval  hibernation  must  be 
extremely  common.  MitchelP^^  found  anopheles  larvae  in  tanks 
and  barrels  in  the  Botanical  Gardens  of  Washington,  D.  C, 
during  winter,  and  Woldert"'^^  found  these  larvae  in  December  at 
Tyler,  Texas. 

Mitchell^^^  beHeves  it  probable  that  mosquitoes  do  not  hiber- 
nate in  the  pupal  stage,  though  GalH-Valerio  and  De  Jongh'**" 
maintain  the  opposite  opinion. 

It  is  chiefly  in  the  winged  stage  that  mosquitoes  hibernate. 
In  the  late  fall  the  males  die,  the  fecundated  females  seeking 
shelter  in  dwellings,  cellars,  stables,  barns,  cisterns,  hollow 
trees,  or  under  bridges. 

THE  PARASITES  OF  MALARU 

Zoological  Relations. — The  parasites  of  malaria  belong  to  the 
animal  kingdom,  to  the  division  of  protozoa,  to  the  class  of 
sporozoa,  and  to  the  order  of  hemosporidia.  The  hemocytozoa 
are  not  peculiar  to  man,  but  are  found  in  other  classes  of  verte- 
brates, and  are  distributed  by  Manson-^  into  three  genera,  as 
follows: 


MALARIA                                                            65 

HEMOCYTOZOA 

I. 

Genus 

IL-EMAMCEBA 

Names 

Hosts 

H.  subtertiana. 

The    malaria    parasites    of    man,    the 

H.  quartan. 

sexual  phase  being  evolved  in  mosqui- 

H. tertian. 

toes  of  the  genus  Anopheles. 

H.  relicta  (Proteosoma). 

Birds:  sexual  phase  in  mosquitoes  of 
the  genus  Culex. 

H.  Danielewski  (Halteridium). 

Birds. 

H.  Kochi. 

Several  species  of  monkeys. 

H.  melaniphera. 

Bat  (Miniopterus  Shredeibersii). 

H.  Metchnikovi. 

Trionyx  indicus. 

2. 

Genus  Piroplasma 

P.  bigeminum. 

Bovines:  transmitted  by  the  cattle 
tick  (Boophilus  bovis). 

P.  canis. 

Dogs. 

P.  ovis. 

Sheep. 

P.  equi. 

Horse. 

P.  hominis. 

Man. 

3.  Genus  PLemogregarina 
H.  ranarum  (Drepanidium).  Frog  (Rana  esculenta). 

H.  splendens.  Frog  (Rana  esculenta). 

H.  Magna.  Frog  (Rana  esculenta). 

H.  lacertarum.  Lizard  (Lacerta  muralis). 

About  twenty  additional  but  less  readily  procured  species. 

There  are  three  sharply  defined  species  of  parasites  of  malaria, 
the  parasite  of  tertian  malaria,  the  parasite  of  quartan  malaria, 
and  the  parasite  of  estivo-autumnal  malaria.  The  latter  is 
divided  by  most  observers  into  three,  or  at  least  two,  varieties, 
the  tertian  and  the  quotidian,  of  which  latter  variety  a  pig- 
mented form  and  an  unpigmented  form  are  described.  My 
opinion  is  that  there  are  two  varieties  of  the  estivo-autumnal 
parasite,  the  tertian  and  the  quotidian,  and  that  the  pigmented 
and  the  unpigmented  quotidians  are  merely  forms  of  one  variety. 

Stephens"**^  described  a  form  of  the  parasite  which  he  behaved 
was  a  new  species  and  named  it  Plasmodium  tenue.  It  was  char- 
acterized by  extreme  ameboid  movement,  irregularity  of  form, 
abundance  and  irregularity  of  chromatin  and  an  absence  of 
pigment. 

I  have  recently  obtained  similar  specimens  from  a  case  of 
s 


66  ENDEMIC   DISEASES    OF    THE    SOUTHERN    STATES 

comatose  malaria  and  believe  that  this  organism  is  an  atypical 
form  of  estivo-autumnal  parasite. 


\ 


ill' 

\ 

11 

\ 

M 

/^ 

^ 

#^- 

V 

Fig.  20. — Diagram  illustrating  the  cycles  of  the  parasite. 
— .  — .  — .  — .    Schizogonic  cycle. 

Sporogonic  cycle. 

Paithenogenetic  cycle. 

Biology. — The  life  history  of  the  parasites  of  malaria  is  some- 
what complicated,  inasmuch  as  man,  the  mosquito,  and  the 
parasite  are  involved,  and  as  there  are  three  species  of  parasites 
and  each  species  has  three  biologic  cycles.  These  three  cycles 
are: 


MALARIA  67 

I.  The  schizogonic,  or  human  cycle,  also  called  the  asexual 
cycle,  monogonic  cycle,  endogenous  cycle,  cycle  of  Golgi, 
or  trophic  cycle. 


Fig.  21. — The  entrance  of  the  sporozoit  into  the  red  cell. 

2.  The  sporogonic  or  mosquito  cycle,  also  called  the  sexual 
cycle,  amphigonic  cycle,  exogenous  cycle,  or  cycle  of  Ross. 

3.  The  parthenogenetic  cycle,  or  reproduction  by  unfertil- 
ized macrogametes ;  the  cycle  of  chronic  malaria,  of  latency  and 
relapses,  an  immaculate  conception  yielding  saviors  to  the 
species  necessary  for  its  salvation  at  a  time  of  crisis,  a  vicarious 
atonement  of  macrogametes  that  the  human  cycle  may  be 
saved. 

The  first  cycle  is  that  of  active  malaria;  the  last  two  are  des- 
tined for  the  perpetuation  of  the  species,  and  without  them  the 
interruption  of  the  schizogonic  cycle  would  result  in  the  ex- 
termination of  the  species. 

The  Schizogonic  Cycle. — In  the  act  of  biting,  the  mosquito 
injects  into  the  blood  sporozoits,  elongated  or  needle-shaped 
organisms.  The  sporozoits  have  the  power  of  bending,  con- 
traction, and  of  locomotion,  and  each  immediately  penetrates 
into  a  red  blood-cell.  Here  it  loses  its  slender  form  and  appears 
as  a  mere  dot  of  protoplasm,  whose  index  of  refraction  varies 
but  little  from  that  of  the  red  blood-cell.  The  size  of  the  young 
parasite  varies  in  different  species,  but  is  about  i  or  2  microns 
in  diameter.  Ameboid  motion  is  more  or  less  active,  pseudo- 
podia  being  protruded  and  retracted,  the  parasite  even  changing 
its  position  within  the  cell,  and  has  no  constant  form.  There  is 
usually  only  one  parasite  in  each  infected  cell,  but  there  may  be 
several.  As  the  parasite  grows  it  acquires  pigment,  a  few 
grains  at  first,  gradually  increasing  in  amount  with  the  growth 
of  the  parasite.     This  pigment  is  from  the  hemoglobin  of  the 


68 


ENDEMIC   DISEASES    OF   THE    SOUTHERN    STATES 


infected  cell,  and  occurs  in  the  form  of  grains,  rods,  or  clumps. 
The  adult  parasite  occupies  a  relatively  large  portion  of  the  cell, 
and  ameboid  motion  is  less  active,  though  the  pigment  may  be 
in  violent  motion.  The  organism  is  composed  of  cell  proto- 
plasm, nucleus,  and  nucleolus,  but  appears  structureless  in  fresh, 
unstained  blood.  Prior  to  sporulation  the  pigment  becomes 
concentrated  and  fused,  and  fission  occurs,  dividing  the  para- 
site more  or  less  symmetrically  into  spores,  constituting  the 


Fig.  22. — Diagram  representing  the  development  of  the  malarial  parasite:  a, 
Young  form;  b,  half-grown  parasite;  c,  sporulating  body;  d,  free  spores;  e, 
macrogamete;/,  microgametocyte. 


so-called  rosette  or  marguerite  forms,  each  spore  containing  a 
fragment  of  nucleus.  The  cell  ruptures  and  the  spores,  or 
merozoites,  escape  into  the  blood  current,  where  they  rapidly 
enter  the  blood-cells  to  repeat  the  cycle.  The  corpuscular 
remnants  and  the  pigment  are  rapidly  taken  up  by  the  phag- 
ocytes. 

Rowley-Lawson'*^*'  has  attempted  to  prove  that  the  malaria 
parasite  is  extracellular  throughout  its  life  cycle,  migrating  from 
cell  to  cell,  destroying  each  before  it  is  abandoned,  and  that  in 
the  brief  intervals  between,  the  parasite  is  free  in  the  blood 
serum.  These  observations  have  not  been  confirmed;  on  the 
other  hand  the  experiments  of  Bass  and  Johns^^"  seems  to  over- 
throw them. 

Instead  of  proceeding  to  sporulation  some  of  the  parasites 
develop  into  sexual  forms,  or  gametes,  large  parasites  of  round, 
ovoid,  spindle,  or  crescentic  shape.  It  is  these  bodies  which 
are  taken  up  by  the  mosquito,  undergo  a  sexual  cycle  in  its 
midgut,  develop  into  sporozoits,  which  are  injected  into  man, 


MALARIA  69 

where  they  pass  through  the  schizogonic  cycle  above  outlined. 

The  Tertian  Parasite  {Hcemamceba  vivax,  H.  tertiance, 
Plasmodium  vivax). — The  duration  of  the  asexual  cycle  of  the 
simple  tertian  parasite  is  forty-eight  hours.  The  young  para- 
sites are  about  one-fifth  the  size  of  the  red  blood  corpuscles  and 
unpigmented.  They  are  difficult  to  distinguish  from  the  young 
parasites  of  the  other  species.  They  are  actively  ameboid, 
protruding  and  retracting  short  pseudopodia  with  rapidity; 
Y-shapes,  T-shapes,  and  crosses  are  common  forms.  The  index 
of  refraction  of  the  parasites  is  low,  so  that  their  contours  are 
not  easily  distinguished  from  the  substance  of  the  red  blood-cells. 
As  the  parasite  increases  in  size  pigment  gradually  appears. 
The  pigment  of  the  tertian  parasite  is  fine,  rod-shaped,  rather 
light  in  color,  and  in  active  motion.  This  motion  of  the  pig- 
ment has  been  compared  to  the  bubbling  of  boiling  water  and  to 
the  swarming  of  insects.  The  infected  red  cell  becomes  enlarged, 
swollen  and  pale.  The  half-grown  parasite  fills  about  half  or 
two-thirds  of  the  red  blood  corpuscle.  At  this  stage  the  para- 
site assumes  fantastic  and  bizarre  shapes.  The  adult  parasite 
is  more  or  less  spherical,  as  large  as  or  larger  than  a  normal 
red  cell,  and  occupies  three-fourths  or  four-fifths  of  the  swollen 
infected  cell,  the  margin  of  which  may  be  difficult  to  see  on 
account  of  its  pale  color.  The  pigment  tends  to  become  more 
abundant  about  the  periphery.  When  sporulation  is  immi- 
nent the  parasite  and  its  pigment  become  less  active  or  motion- 
less, the  pigment  gathers  in  clumps  at  the  center,  and  radial 
striations  appear  from  the  periphery  toward  the  center.  Usu- 
ally the  sporulating  tertian  parasite  is  not  so  symmetrical  as  the 
corresponding  stage  of  the  quartan,  resembling,  rather,  a  bunch 
of  grapes  or  a  mulberry.  Less  often  there  are  two  concentric 
rows  of  spores.  The  spores  are  small  and  vary  in  number  from 
twelve  or  fourteen  to  twenty-six,  oftenest  sixteen,  and  more 
often  an  even  than  an  uneven  number.  Sporulation  takes 
place,  especially  in  the  circulation  of  certain  viscera,  but  sporu- 
lating tertian  parasites  are  much  more  frequently  encountered 
in  the  peripheral  circulation  than  in  the  case  of  estivo-autumnal 
infections. 

The  parasites  develop  with  remarkable  uniformity,  nearly  all 


yo  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

appearing  to  be  of  the  same  age.  Even  in  infections  with  two 
groups  of  tertian  parasites,  which  is  very  common,  it  is  unusual 
to  find  a  parasite  which  does  not  belong  to  one  brood. 

The  early  development  of  the  gametes  is  not  well  understood. 
Half-grown  gametes  are  hard  to  differentiate  from  schizonts, 
but  small  parasites,  without  ameboid  motion,  with  much  pig- 
ment, and  with  large  nucleus  may  be  twice  as  large  as  a  red 
blood  corpuscle.  Ameboid  movement  is  very  slight.  The  pig- 
ment is  profuse,  fine,  reddish,  or  blackish,  and  actively  motile. 
The  vesicular  appearing  nucleus  is  commonly  situated  near  the 
periphery,  and  is  visible  in  fresh  preparations. 

An  interesting  phenomenon  which  occurs  in  the  case  of  the 
microgametocytes,  or  male  sexual  forms,  is  exflagellation. 
This  takes  place  from  ten  to  thirty  minutes  after  the  blood  has 
been  withdrawn,  and  is  favored  by  exposing  the  blood  for  a  few 
minutes  to  the  air,  by  the  addition  of  a  minute  quantity  of  water, 
and  exposure  to  moisture,  as  breathing  upon  the  slide  before 
applying  the  cover-glass.  Before  exflagellation  the  pigment  is 
observed  to  undergo  violent  and  tumultuous  motion,  then  to 
collect  toward  the  center.  Undulations  at  the  periphery  are 
then  noticed,  as  if  something  within  were  trying  to  escape. 
Suddenly  the  flagella  break  forth  from  different  points  of  the 
margin.  These  are  from  four  to  eight  in  number  and  in  length 
are  two  and  a  half  to  three  times  the  diameter  of  the  red  blood 
corpuscle.  They  may  show  ovoid  swellings  at  the  end  or  in 
their  continuity.  Lashing  madly  to  and  fro,  the  red  cells  are 
displaced  and  a  fiagellum  may  be  seen  to  break  off  from  the 
microgametocyte  and  dart  in  a  serpentine  manner  among  the 
cells.  The  flagella  are  known  as  microgametes,  and  have  been 
shown  by  McCallum  to  be  spermatozoa.  Their  function  is  to 
fertilize  the  macrogametes,  or  female  forms,  in  the  midgut  of 
the  mosquito. 

Tertian  gametes  may  be  distinguished  from  adult  schizonts 
by  the  former  being  of  larger  size,  less  ameboid  motion,  their 
pigment  appearing  earlier,  being  more  abundant  and  in  more 
active  motion. 

The  following  may  serve  to  differentiate  tertian  male  and 
female  gametes: 


DESCRIPTION   OF   PLATES   I   AND   11 


Various  forms  of  malarial  parasites:  Figs,  i  to  lo  inclusive,  tertian  parasites; 
Figs.  II  to  19  inclusive,  quartan  parasites;  Figs.  20  to  26  inclusive,  estivo- 
autumnal  parasites. 

I. — Normal  red  blood  cell.  2. — Young  tertian  ring.  3. — Large  tertian  ring. 
4. — Half-grown  tertian  parasite.  5. — Infected  cell  showing  Schiiffner's  dots. 
6. — Adult  tertian  parasite.  7. — Beginning  sporulation.  8. — Sporulation  com- 
pleted. 9. — Tertian  microgametocyte.  10. — Tertian  macrogamete.  11. — Young 
quartan  ring.  12. — Older  quartan  ring.  13. — Quartan  band.  14. — Older 
quartan  band.  15. — Full-grown  quartan  parasite.  16. — Mature  parasite  with 
divided  chromatin.  17. — Sporulation  completed.  18. — Quartan  microgameto- 
C3'te.  19. — Quartan  macrocyte.  20. — Young  estivo-autumnal  ring.  21. — Large 
estivo-autumnal  ring.  22. — Mature  parasite.  23. — Sporulation  completed. 
24. — Estivo-autumnal  microgametocyte.  25. — Estivo-autumnal  macrogamete. 
26. — Estivo-autumnal  ovoid. 


■ .,  '"#4 


PLATE   I 


O 


mi 


.AiCdb^^ 


o 


Q 


16 


PLATE    11 


»«i^ 


13 


14 


o 


o 


23 


21 


■  *<!'*  » +4,: 


MALARIA  7 1 

Microgameiocytes  M  acrogaineles 

Plasma  hyaline.  Plasma  granular. 

Pigment  abundant  in  thick  rods,  Pigment   in    fine    rods    and    granules, 

brownish  yellow.  brownish  black. 

Not  larger  than  a  red  blood-cell.  Larger  than  red  cell. 

Chromatin  profuse.  Chromatin  less  abundant. 

Little  ameboid  motion.  More  or  less  ameboid  motion. 

Nucleus  toward  center.  Nucleus  toward  periphery. 

In  stained  films  the  early  stage  of  the  tertian  parasite  is  seen 
as  a  ring.  Often  the  ring  is  not  of  the  same  thickness  through- 
out its  circumference,  but  is  composed  of  a  thin  segment,  and  a 
thicker  segment,  the  chromatin  being  upon  the  thin  segment. 
Usually  the  chromatin  dot  is  immediately  within  the  ring,  but 
it  may  lie  outside,  and  is  surrounded  by  a  pale  zone.  The 
achromatic  zone  may  b°e  regarded  as  the  nucleus  and  the  chro- 
matin as  the  nucleolus.  As  the  parasite  develops  one  arc  be- 
comes much  thickened,  giving  the  appearance  of  the  signet  ring. 
The  forms  of  the  half-grown  parasites  are  varied  and  peculiar. 
Pigment  appears  first  and  most  abundantly  in  the  peripheral 
region,  and  does  not  invade  the  clear  zone.  The  red  cell  is 
enlarged  and  does  not  stain  deeply.  A  peculiar  stippling  of  the 
infected  red  cells  is  shown  in  films  containing  tertian  parasites 
and  stained  with  the  Romanowsky  stain  or  one  of  its  modifica- 
tions. When  the  parasite  fills  one-third  of  the  cell  a  number  of 
fine,  red-stained  points,  Schiiffner's  dots,  appear,  which  increase 
in  size  but  not  in  number  as  the  parasite  grows.  In  the  process 
of  sporulation  the  chromatin  becomes  subdivided  and  sur- 
rounded by  a  clear  zone,  and  encircled  by  the  blue  cytoplasm, 
constituting  the  spore. 

The  Quartan  Parasite  {Hcsmamwba  malarice,  H.  qiiartanw, 
Plasmodium  malarice,  Laverania  malarice). — The  duration  of  the 
schizogonic  cycle  of  the  quartan  parasite  is  seventy-two  hours. 
The  young  forms  of  the  parasite  appear  as  small,  hyaline,  un- 
pigmented  bits  of  protoplasm.  They  are  highly  refractive  and 
the  contour  is  much  more  sharply  defined  than  the  tertian  para- 
site. Ameboid  motion  is  sluggish  and  the  organism  may  be 
watched  sometime  until  motion  is  detected.  Pigment  appears 
within  twenty-four  hours.  It  is  in  larger  quantities  than  in  the 
tertian  parasite,  in  coarser  grains  or  rods,  and  dark  brown  or 


72  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

black  in  color.  The  pigment  is  accumulated  around  the  mar- 
gin, and  its  motion  is  very  slow.  In  the  half-grown  parasites 
the  pecuh'ar  forms  observed  in  the  tertian  organisms  are  not 
seen,  and  ameboid  movements  become  more  sluggish  or  cease 
altogether.  The  red  blood-cell  infested  with  the  quartan  para- 
site does  not  enlarge  and  decolorize  as  in  tertian  infections,  but, 
if  there  is  any  deviation  from  normal,  becomes  smaller  and 
darker,  perhaps  greenish  and  brassy.  The  adult  parasites  are 
almost  as  large  as  the  red  cells.  Prior  to  sporulation  the  pig- 
ment collects  toward  the  center,  often  in  a  radial  arrangement. 
Sporulation  proceeds  after  the  manner  of  the  tertian  parasite, 
but  is  slower.  The  sporulating  forms  are  beautifully  symmetrical 
and  are  typical  rosettes.  The  spores  are  round  or  oval,  rela- 
tively large  and  six  to  twelve  in  number,  oftenest  eight.  Sporu- 
lating quartan  parasites  are  much  more  commonly  observed  in 
the  peripheral  blood  than  are  the  corresponding  forms  of  the 
other  species. 

Quartan  gametes  are  but  rarely  encountered.  The  macro- 
gametes  are  spherical  in  shape,  and  as  long  as  they  remain  in- 
tracorpuscular  are  smaller  than  tertian  gametes,  but  are  equally 
as  large  when  they  become  extracorpuscular.  Exflagellated 
microgametocytes  have  been  observed;  they  are  somewhat 
smaller  than  the  tertian  forms,  but  no  less  active. 

The  staining  reactions  of  the  quartan  parasites  are  similar  to 
those  of  the  tertian.  The  young  form  is  a  ring  and  so  closely 
resembles  the  tertian  that  it  cannot  be  determined  with 
certainty.  After  twelve  to  twenty-four  hours  the  parasite 
becomes  disc-  or  band-shaped.  The  latter  forms  are  character- 
istic. The  parasite  extends  across  the  center  of  the  infested  cell 
as  a  more  or  less  broad  band,  often  rather  quadrilateral,  the 
pigment  being  arranged  more  profusely  along  the  margin  of  the 
band.  The  chromatin  body  of  the  quartan  species  stains  less 
intensely  and  splits  earher  than  the  tertian.  The  adult  usually 
fills  the  corpuscle,  which  may  be  no  longer  apparent.  The 
sexes  of  the  gametes  are  differentiated  by  the  same  characters 
as  in  the  tertian. 

The  Estivo-autxmmal  Parasite  {Hamamceba  pracox,  Plas- 
modium  prcEcox,    Hamamceha   immaculata,   Laverania   prcecox, 


MALARIA  73 

Hamomenas  pracox,  Plasmodium  immacutatum,  Hmmamozba 
parva,  Hamatozoon  falciform,  Plasmodium  falciparum). — The 
young  forms  of  the  estivo-autumnal  parasites  are  similar  to 
those  of  the  other  species,  but  are  smaller,  being  from  one-fifth 
to  one-sixth  the  size  of  the  infested  corpuscle.  Ameboid  motion 
is  rather  active,  stars,  crosses,  and  irregular  shapes  occurring  in 
succession.  At  rest  the  parasites  appear  annular  or  discoid. 
More  than  one  parasite  in  a  single  cell  is  relatively  more  com- 
mon than  in  tertians  and  quartan  infections.  Advanced  stages 
of  development  are  rarely  seen  in  peripheral  blood.  The  in- 
fested red  cells  often  become  shriveled,  crenated,  darker,  and  of 
a  brassy  hue.  The  adult  parasites  do  not  attain  the  size  of  the 
red  blood  corpuscles.  Sporulation  proceeds  in  a  manner  simi- 
lar to  that  of  the  simple  tertian  parasite.  The  spores  number 
from  five  to  twenty-five  or  even  thirty.  Sporulation  is  not  so 
uniform  as  in  other  infections;  sporulating  forms  may  be  associ- 
ated with  young  or  half-grown  parasites. 

Estivo-autumnal  gametes  occur  in  the  form  of  crescents,  and 
of  fusiform,  ovoid,  and  spherical  bodies.  The  crescents  are 
characteristic,  being  found  in  this  form  of  malaria  alone.  They 
are  cylindrical,  tapering  shghtly  at  each  extremity,  and  slightly 
curved  upon  themselves.  They  are  longer  than  the  diameter 
of  the  red  cell  and  about  a  third  as  broad  as  long.  The  changes 
from  crescent  to  ovoid  and  round  bodies  may  be  easily  observed 
under  the  microscope.  The  gametes  appear  only  after  the 
infection  has  persisted  for  about  a  week.  The  crescent  may  lie 
within  the  cell  or  may  have  the  appearance  of  the  red  cell  being 
attached  to  the  concave  side;  in  some  instances  there  is  no  evi- 
dence left  of  the  infested  blood-cell.  The  cell  may  be  stretched 
across  the  concavity  of  the  crescent,  and  is  usually  almost  decol- 
orized. The  crescents  have  given  evidence  of  a  double  outline. 
They  possess  no  ameboid  movement,  and  the  pigment  in  the 
form  of  rods  or  granules  is  motionless.  Before  exflagellation 
the  crescent  assumes  the  spheric  form,  smaller  than  the  tertian, 
and  similar  to  the  quartan. 

The  staining  reactions  of  the  estivo-autumnal  schizonts  are 
similar  to  those  of  the  tertian  and  quartan.  The  young  para- 
sites are  unpigmented  rings,  resembling  the  simple  tertian  rings, 


74 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


but  are  smaller  and  more  delicate.  Typical  signet  rings  and 
rings  without  nodes  are  seen.  The  ring  may  be  distorted  or 
become  broken  and  extended  like  a  delicate  thread  or  a  narrow 
band.  The  largest  rings  are  about  one-half  the  diameter  of  the 
red  cell.  The  pigment  is  sparse.  Both  the  sporulating  b'ody 
and  the  individual  spores  are  small.  The  central  region  of  the 
crescent  is  almost  achromatic,  the  extremities  staining  more 
deeply.  Chromatin  is  not  always  visible  in  the  crescents,  but 
is  usually  seen,  as  is  the  pigment,  in  the  achromatic  area. 

Mixed  infections  with  quotidian  and  tertian  estivo-autumnal 
parasites  are  very  common. 

The  differences  between  these  parasites  are  thus  tabulated  by 
Craig:"" 

The  Hyaline  Body 


Stage  o£ 
development 

Quotidian 

Malignant  tertian 

Size 

Minute,  one-sixth  of  corpuscle. 

Larger,  one-third  to  one-quarter 
of  corpuscle. 

Shape 

Ring  or  perfectly  round. 

Signet-ring  shape. 

Outline 

Indistinct. 

Clear  cut  and  refractive. 

Motion 

Very  active. 

Sluggish. 

Corpuscle.  . 

Very     dark     green,     wrinkled. 
Crenated. 

Light  green,  less  wrinkled. 

Number. .  .  . 

More  than  one  parasite  in  a  cor- 

Very seldom  more  than  one  par- 

puscle, common. 

asite  in  a  corpuscle. 

The  Pigmented 

Body 

Size 

One-quarter  size  of  corpuscle. 

One-half  size  of  corpuscle. 

Shape 

Round.     Loses  ring  form  before 

Ring  form  becomes  pigmented; 

pigmentation. 

afterward  the  parasite  is  round. 

Motion 

Ameboid  motion  is  lost. 

Ameboid  motion  continues.  Is 
sluggish. 

Outline 

More  sharply  defined. 

Very  sharply  defined  and  refrac- 
tive. The  protoplasm  firmly 
granular. 

Pigment. . .  . 

One  or  two  coarse  granules  per- 

Several minute  grains  having  a 

fectly  motionless. 

rapid  vibratory  motion. 

Number. .  .  . 

May  be  more  than  one  in  a  cor- 

Never more  than  one  in  a  cor- 

puscle. 

puscle. 

Corpuscle. 

Very  green  in  color,  often  cre- 
nated. 

Lighter  in  color,  seldom  crenated. 

MALARIA 
The  Segmented  Body 


75 


Place  of  seg- 

Within the  red  blood  corpuscles, 

Outside  the  red  blood  corpuscles 

mentation. 

as  a  rule. 

as  a  rule. 

Number   of 

Six  to  eight. 

Ten  to  fifteen  or  more. 

segments. 

The  crescent 

Crescents  small  and  plump,  con- 

Crescents long,  narrow,  deeply 

phase. 

taining  small  amount  of  pig- 

pigmented. Double  outline  less 

ment.     Always  present  double 

common. 

outline. 

Cycle  of  de- 

Twentv-four hours. 

Forty-eight  hours. 

velopment. 

The  following  table  will  serve  to  distinguish  the  sexes  of  the 
gametes: 

M  icrogametocyies  Macrogametes 

Protoplasm  stains  very  slightly.  Protoplasm  stains  more  intensely. 

Pigment   distributed   throughout   the      Pigment  collected  near  center  often  in  a 
parasite.  circle. 

Reniform  short  and  broad.  Crescentic,  longer  and  narrower. 

Chromatin  in  several  scattered  masses.     Chromatin  in  one  or  two  large  masses 

near  the  center. 
The  chief  characteristics  of  the  species  of  malaria  parasites 
may  be  tabulated  as  follows: 


Tertian 

Quartan 

Estivo-autumnal 

Length  of  asex- 

Forty-eight hours.     Seventy-two  hours. 

Twenty-four  hours. 

ual  cycle. 

! 

forty-eight  hours, 
or  irregular. 

Site  of  sporula- 

May   sporulate   in    Equally  in  peripheral 

Visceral       circula- 

tion. 

peripheral  blood,      and  visceral  blood. 

tion. 

chiefly  in  visceral 

circulation. 

Movements. 

Active. 

Sluggish. 

Active. 

Pigment. 

Fine,  yellowish  or 

Coarse,  dark  brown  or 

Scanty,  fine. 

dark  brown,  scat- 

black, (at  periphery), 

tered,        actively 

slightly  motile. 

motile. 

Effect   on   red 

Enlarged,  decolor- 

Normal size  or  smaller, 

Often      shrunken, 

cell. 

ized,     Schiifiner's 

often       dark       and 

may  be  dark  and 

dots    in    stained 

brassy. 

brassy. 

films. 

Size  of  adult. 

As  large  as  normal 

Smaller   than    normal 

Much  smaller  than 

red  corpuscles. 

corpuscles.                    '    normal  corpuscles. 

Sporocyte. 

Mulberry  shape.      i  Symmetrical         daisy    Irregular. 

shape.                            1 

Spores. 

12-26,  oftenest  16. 

6-12,  oftenest  8.              5-30- 

Gametes. 

Spheric. 

Spheric.                              Crescentic. 

76  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

It  is  not  infrequently  difficult  to  differentiate  young  tertian 
from  young  estivo-autumnal  rings,  though  the  following  table 
adapted  from  Ewing^^^  will  enable  a  comparison  of  the  main 
feature : 

Tertian  Estivo-autumnal 

Nucleus  achromatic  to  methylene-blue.     Nucleus  stains  intensely  with  methyl- 

ene-blue. 
Ring  usually  coarse  and  irregular.  Ring  geometrically   circular,   delicate, 

usually  a  typical  signet-like  swelling. 
One  or  two  grains  of  pigment  almost      Pigment  almost  constantly  absent, 
invariably  present. 
Ring  usually  pigmented  before  chro-      Chromatin  always    subdivides    before 

matin  subdivides.  pigment  appears. 

Infected  cell  swollen.  Infected  eel!  shrunken.. 

The  Sporogonic  Cycle. — If  the  anopheline  mosquito  obtains 
blood  containing  only  schizonts,  the  latter  soon  perish  in  the 
digestive  canal  of  the  insect.  However,  if  the  blood  contains 
mature  gametes  of  both  sexes  these  undergo  the  exogenous  cycle, 
to  be  prepared  to  reinfect  man  bitten  by  the  infected  mosquito. 
The  portion  of  the  mosquito  in  which  this  transformation  takes 
place  is  the  stomach  or  midgut.  Shortly  after  the  infested 
blood  has  been  sucked  into  the  stomach  the  microgametocytes 
exfiagellate,  the  microgametes  become  free,  and  the  macro- 
gametes  emit  small  protuberances  to  receive  the  flagella  or  sper- 
matozoa. The  latter  forces  an  entrance  into  the  macrogamete 
at  the  site  of  the  protuberance  and  the  resulting  fertilized 
body  is  known  as  the  zygote.  All  this  has  taken  place  within 
the  first  few  hours.  In  its  early  stages  the  zygote  resembles  the 
ovoid  body,  but  is  larger.  It  is  pigmented,  it  enlarges,  becomes 
pyrif orm,  and  has  the  p.ower  of  locomotion.  The  zygote  burrows 
through  the  epithelial  coat  of  the  midgut  to  the  tunica  elastico- 
muscularis,  becomes  spheric  and  encysted,  and  is  known  as  the 
oocyst.  It  enlarges  so  that  it  projects  like  a  spheric  excres- 
cence into  the  body  cavity  or  blood  sinus,  where  it  is  nourished. 
The  stomach  of  a  badly  infected  mosquito  may  be  studded  with 
these  outgrowths.  The  oocyst  attains  a  size  of  40  to  70  microns 
in  diameter.  Its  nuclear  chromatin  divides  and  subdivides, 
each  portion  surrounded  by  protoplasm,  polygonal  or  irregular 
in  shape  from  pressure,  being  known  as  the  sporoblast.     Each 


MALARIA  77 

sporoblast  splits  into  a  large  number  of  sporozoits,  each  enclos- 
ing a  bit  of  chromatin.  The  sporozoits  remain  attached  by  one 
end  to  the  residual  body  of  the  sporoblast  until  the  oocyst  bursts, 
when  the  sporozoits  escape  into  the  body  cavity.  Finally 
through  the  lacunar  circulation,  they  arrive  at  the  salivary 
glands,  where  they  congregate  in  hordes.  The  sporozoits 
number  from  a  few  hundreds  to  ten  thousand  or  more.  Each 
measures  about  14  microns  in  length,  about  eight  times  as  long 
as  broad,  being  very  slender,  tapering  at  both  ends,  and  endowed 
with  serpentine  movements.  From  the  salivary  glands  the 
sporozoits  are  injected  by  the  mosquito,  in  the  act  of  preying 
upon  its  victim,  where  each  sporozoit  soon  enters  a  red  cell  and 
goes  through  the  schizogoniq  cycle.  The  duration  of  the  mos- 
quito cycle  varies  from  eight  to  sixteen  or  more  days,  depending 
mainly  upon  the  temperature,  but  possibly  also  upon  other 
factors. 

The  three  species  of  parasites  are  closely  similar  in  their 
stages  of  exogenous  development.  The  differences  between  the 
tertian  and  the  estivo-autumnal  organisms  are  that  in  the  former 
the  zygote  is  round  or  oval  instead  of  pyriform  or  ovoid,  the 
protoplasm  is  less  refractive,  the  characteristic  pigment  main- 
tains, the  sporoblasts  are  larger  and  less  numerous,  the  sporo- 
zoits are  less  dense  and  more  regularly  arranged,  often  radially 
within  the  sporoblast,  and  black  spores  have  not  been  found. 

The  quartan  parasite  is  the  most  difficult  to  develop  within 
the  mosquito. 

The  Parthenogenetic  Cycle. — Parthenogenesis,  or  virgin 
birth,  is  reproduction  by  unfertilized  females. 

This  phenomenon,  known  also  as  the  "alternation  of  genera- 
tions," has  been  most  carefully  studied  in  plant  lice,  the 
Aphidce.  The  eggs,  which  are  laid  in  the  fall  and  have  hiber- 
nated, hatch  in  the  spring  into  females,  having  the  power  of 
giving  birth,  without  fertilization,  to  viviparous  young,  which 
inherit  the  faculty  of  parthenogenesis,  and  procreate  in  this 
manner  until  the  advent  of  cold  weather  or  the  failure  of 
nourishment  when  males  and  oviparous  females  are  brought 
forth.  From  these  latter,  after  copulation,  ova  are  produced, 
and  the  cycle  recommences. 


78  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Parthenogenetic  reproduction  is  known  to  occur  in  a  number 
of  species,  as  hemoproteus,  certain  rotifera,  jellyfish,  worms, 
entomostracea,  acarina,  and  certain  insects,  the  silk-moth, 
mosquitoes,  gall-flies,  ants,  bees,  wasps,  chironomus,  etc. 

This  life  cycle  of  the  parasite  of  malaria  is  the  most  recently 
recognized  and  least  known  of  its  cycles.  Since  the  discovery 
of  the  parasite  the  gametes  have  been  regarded  as  closely  allied 
with  the  chronic  malaria  and  relapses.  Golgi  plainly  stated  as 
his  belief  that  the  crescent  was  the  parasite  of  fevers  recurring 
at  long  intervals. 

Canalis,'*^^  in  1889,  described  and  pictured  spheric  bodies 
derived  from  crescents  in  the  act  of  sporulation.  In  1890, 
Antolisei  and  Angelini*^^  confirmed  the  observation  of  Canalis. 
Lewkowicz^'^  reported,  in  1897,  that  he  had  seen  sporulating 
crescents  some  of  which  contained  as  many  as  thirty  spores. 

Grassi*^*  expressed  the  opinion  in  1901  that  the  parasites  of 
malaria  underwent  a  parthenogenetic  cycle  of  development 
whereby  the  species  was  perpetuated  after  the  death  of  the 
schizonts. 

He  cited  a  number  of  arguments  in  support  of  the  theory,  and 
referred  to  a  similar  process  in  other  protozoa,  Adelea,  Tricho- 
sphcBrium,  and  Volvox. 

It  was  Schaudinn''^'*  who,  in  1902,  first  observed  and  correctly 
interpreted  parthenogenesis  of  tertian  macrogametes,  and  who 
thus  describes  the  process  of  parthenogenesis  as  he  observed 
it  in  tertian  malaria.  The  chromatin  of  the  parthenogametes 
collects  in  coarse  fragments  and  cords  toward  one  end  of  the 
bean-shaped  nucleus,  and  stains  intensely,  while  the  other  some- 
what larger  half  contains  fewer  and  smaller  chromatin  par- 
ticles and  stains  faintly.  The  nucleus  then  divides  into  two, 
one  containing  the  coarse,  deeply  staining  chromatin,  and  the 
other  the  fine,  diffusely  staining  chromatin,  the  former  resemb- 
ling the  nucleus  of  a  schizont  before  nuclear  proliferation.  A 
constriction  may  be  perceptible  about  the  parasite  almost  sepa- 
rating a  deeply  staining,  highly  pigmented  portion  containing 
the  pale  staining  nucleus  from  a  lightly  stained  and  less  pig- 
mented portion  in  which  lies  the  deeper  stained  nucleus.  This 
nucleus  now  subdivides  and  the  portion  of  the  plasma  in  which 


MALARIA  79 

it  lies  proceeds  to  sporulation  in  a  manner  similar  to  schizogonic 
sporulation,  the  spores  becoming  typical  schizonts. 

Maurer/^^  in  1902,  observed  sporulation  of  estivo-autumnal 
gametes,  and  construed  it  as  parthenogenesis. 

Ziemann^^  beheves  that  he  has  seen  parthenogenetic  repro- 
duction of  quartan  gametes. 

Bluml  and  Metz'*'®  observed  sporulating  parthenogametes 
in  six  preparations  taken  from  five  patients  with  tertian  malaria. 


Fig.  23. — Parthenogenesis  of  the  tertian  parasite  (after  Schaudinn). 

The  process  was  identical  with  that  described  by  Schaudinn. 
Young  and  sporulating  schizonts  and  young  gametes  were 
present  in  these  same  preparations. 

Bass  and  Johns^°°  observed  a  process  resembling  partheno- 
genesis in  some  of  their  cultivation  experiments. 

Are  the  parthenogametes  identical  with  true  macrogametes 
which  do  not  proceed  to  sporulation?  Such  a  doubt  is  hardly 
justifiable  from  a  review  of  the  scientific  studies  of  the  learned 
Schaudinn  and  of  the  other  observers  cited  above.     Craig/'' 


8o  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

however,  has  recently  adduced  evidence  that  latency  and  re- 
lapses are  dependent  upon  resting  bodies,  the  products  of  intra- 
corpuscular  conjugation  of  young  schizonts.  He  does  not, 
however,  follow  these  forms  further  than  the  completion  of  con- 
jugation, and  while  it  is  possible  that  this  is  the  origin  of  the 
parthenogametes,  there  is  as  yet  no  positive  evidence  that  the 
latter  are  not  true  macrogametes. 

Ctiltivation  Experiments. — Coronado*^^  claimed  to  have  been 
successful  in  cultivating  the  malarial  parasites  from  water  which 
he  beheved  infected.  He  stated  that  the  entire  cycle  could 
be  followed.  Miller^^  also  believed  that  he  had  cultivated  the 
organisms.  These  experiments  have  been  repeated,  but  the 
results  could  not  be  confirmed,  hence  were  probably  incorrect. 

Sakharov,  Rosenbach,  Blumer,  Hamburger  and  Mitchell ""^^ 
succeeded  in  maintaining  the  organisms  alive  for  several  days 
in  the  bodies  of  leeches  which  had  sucked  the  blood  from  malarial 
patients. 

In  1 91 1,  Bass^^^  announced  the  successful  cultivation  of  the 
three  varieties  of  malarial  parasites.  The  technic  as  developed 
by  Bass  and  Johns^''"  may  be  summarized  as  follows: 

The  blood  is  collected  from  the  patient's  vein  at  the  bend  of 
the  elbow,  unnecessary  exposure  to  air  and  agitation  being 
avoided.  One-tenth  of  a  cubic  centimeter  of  a  50  per  cent, 
solution  of  dextrose  for  each  10  c.c.  of  blood  to  be  taken  is 
placed  in  the  defibrinating  tube  before  the  blood  is  drawn. 
The  blood  is  defibrinated  by  gently  stirring  or  whipping  with 
a  glass  rod,  care  being  taken  not  to  whip  in  air  or  cause 
bubbles. 

The  column  of  blood  must  be  2.5  to  5  cm.  deep  in  the  tube, 
giving  a  column  of  serum  1.25  to  2.5  cm.  deep  above  the  cells 
after  the  latter  have  settled.  Development  of  the  parasites 
takes  place  at  the  top  of  the  column  of  precipitated  cells,  all 
parasites  below  the  top  layer  dying  in  from  two  to  twenty 
hours.  The  parasites  grow  best  at  an  incubator  temperature  of 
about  40°. 

When  more  than  one  generation  of  parasites  is  to  be  grown  it 
is  necessary  to  remove  the  leucocytes  at  the  time  the  culture  is 
made  in  order  to  avoid  destruction  of  the  organisms  by  them  at 


MALARIA  51 

the  time  of  segmentation.  This  is  done  by  centrifuging  the 
blood  sufficiently  to  force  the  leucocytes  to  the  surface  of  the 
cells,  drawing  off  the  supernatant  serum  and  carefully  pipetting 
the  cells  and  plasmodia  from  about  the  middle  of  the  centrifuged 
mass.  The  latter  are  then  placed  in  the  decanted  serum  and 
incubated. 

Three  successive  generations  sometimes  grow  in  such  a  culture 

|;;:::,  ,  j ::  ::\,.:  y::'::  :...  :  ,  .... 

,.M:    :  ^       ..     :         . 


Fig.  24. — The  relation  between  the  stages  of  the  parasite  and  the  paroxysm. 

but  it  is  usually  necessary,  after  each  segmentation,  to  transfer 
a  portion  of  the  cells  and  parasites  to  a  tube  containing  recently 
prepared  cells  and  serum. 

Only  asexual  forms  have  been  cultivated  but  organisms  sug- 
gesting parthenogenesis  have  been  observed. 

Leucocytes  do  not  attack  intracorpuscular  plasmodia  but  en- 
gulf them  immediately  upon  becoming  free  after  segmentation. 

The  young  parasites  are  soon  destroyed  by  the  serum  and 
enter  fresh  red  cells  only  when  these  lie  in  contact  with  the  cell 
in  which  sporulation  takes  place  and  then  only  at  the  point  of 
juxtaposition. 


82  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Culture  of  parasites  by  this  method  has  been  confirmed  by 
Lavinder,^^^  Ziemann,^"^  Thompson  and  Thompson^^^  and 
others. 

PATHOGENESIS 

Much  fanciful  speculation  had  been  indulged  in  as  to  the 
cause  of  the  paroxysms  until  Golgi  and  others  of  the  Italian 
school  showed  that  it  was  closely  connected  with  the  life  history 
of  the  malarial  parasites. 

The  paroxysm  is  not  immediately  associated  with  the  gradual 
vegetative  growth  of  the  parasite  within  the  corpuscle,  but,  oc- 
curring more  or  less  abruptly  as  it  does,  is  simultaneous  with 
sporulation  and  the  sudden  discharge  into  the  blood  stream 
of  a  new  generation  of  parasites.  In  what  manner  does  this 
process  produce  so  peculiar  a  phenomenon  as  the  malarial 
paroxysm?  Golgi^^  was  of  the  opinion  that  it  was  dependent 
upon  the  entrance  into  fresh  red  cells  of  the  young  generation 
of  parasites.  This,  however,  is  shown  to  be  erroneous  by  the 
fact  that  a  properly  timed  and  adequate  dose  of  quinine  given 
before  the  chill  is  expected  does  not  prevent  the  access  though 
it  does  destroy  the  young  parasites,  preventing  their  invasion 
of  the  cells. 

The  true  explanation  of  the  origin  of  the  paroxysm  is  through 
the  agency  of  a  toxin  Hberated  by  the  sporulative  act.  The 
existence  of  a  toxin,  the  product  of  the  malarial  parasite,  is 
almost  universally  assumed  by  students  of  malaria.  The 
grounds  for  this  assumption  may  be  recounted  as  follows: 

1.  An  analogy  with  other  infectious  diseases. 

2.  Immunity:  this  immunity  is  not  absolute,  but  that  a  rela- 
tive immunity  to  malaria  exists  there  is  no  room  for  doubt. 

3.  The  formation  of  an  antito.xin.  Ford's'*'*  experiments 
being  conclusive  as  to  the  existence  of  such. 

4.  Degenerative  changes  in  the  kidneys,  liver,  spleen,  and 
other  organs  not  otherwise  explainable. 

5.  Blood  changes,  as  anemia  out  of  proportion  to  the  number 
of  parasites,  and  brassy  degeneration,  stippling,  and  poly- 
chromatophiha  of  the  red  cells. 

6.  Increased  toxicity  of  the  urine  and  sweat. 


MALARIA 


7.  The  existence  of  coma  in  malaria  without  parasites  or 
pigment  in  the  brain. 

8.  The  fever  and  its  relation  to  parasitic  sporulation. 

9.  Experimental  proof.  The  negative  results  of  Gualdi,*^ 
Montesano,^^  Mannaberg,^^  and  Celli*''^  are  devoid  of  weight 
against  the  convincing  experiments  of  Rosenau,  Parker,  Francis 
and  Beyer/^^  who  demonstrated  the  existence  in  malarial 
blood  of  a  poison  capable  of  reproducing  the  symptoms  of  the 
disease  when  injected  into  the  veins  of  other  men. 

The  experiments  of  Brown^""  would  seem  to  indicate  that 
the  phenomena  in  human  beings  infected  with  malaria  are,  at 
least  in  part,  directly  referable  to  the  toxic  action  of  the  malarial 
pigment. 

The  parasites  of  tertian  and  quartan  infections  develop  uni- 
formly, one  generation  at  a  time;  hence  typic  paroxysms 
are  the  rule.  Sometimes,  it  is  true,  sporulating  forms  are  met 
with  between  the  accesses,  but  a  certain  dose  of  toxin  is  neces- 
sary to  excite  a  fit.  The  estivo-autumnal  parasites,  on  the  other 
hand,  do  not  sporulate  so  uniformly;  hence  the  poison  is  liber- 
ated in  broken  doses  and  typic  paroxysms  are  more  frequently 
lacking  and  the  fever  more  continuous  or  irregular.  If  sporula- 
tion occurred  more  nearly  simultaneously,  as  in  the  tertian  and 
quartan  forms  of  malaria,  it  is  probable  that  the  sudden  dis- 
charge of  the  more  highly  poisonous  estivo-autumnal  toxin 
would  be  more  often  attended  with  serious  consequences. 
The  uniform  sporulation  of  the  tertian  and  quartan  parasites 
may  be  likened  to  a  body  of  soldiers  firing  by  volleys,  while 
that  of  the  estivo-autumnal  parasites  is  similar  to  soldiers  firing 
at  will. 

The  change  of  type  of  malarial  attacks  has  been  used  as  an 
argument  for  the  unity  of  the  malarial  parasites.  It  is  well 
known,  however,  that  such  occurrences  are  best  explained  by 
a  number  of  different  species.  Quotidian  malarial  paroxysms 
due  to  two  generations  of  tertian  organisms  may  become  tertian 
in  character  by  the  destruction  of  one  generation.  Quotidian 
paroxysms  due  to  a  triple  quartan  infection  may  become 
quartan  or  double  quartan  by  the  death  of  two  generations  or 
of  a  single  generation  of  parasites.     On  the  contrary,  tertian 


g4  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

and  quartan  accesses  may  become  quotidian  by  the  develop- 
ment into  activity  of  one  or  two  additional  generations. 

It  is  remarkable  in  multiple  infections  by  different  genera- 
tions of  the  same  species  of  parasite  that  they  almost  always 
sporulate  on  different  days  and  very  often  about  the  same  time 
each  day.  Thus  it  is  very  rare  in  double  tertian  infections 
that  two  paroxysms  should  occur  within  one  day  followed  by  a 
fever-free  day.  This  is  probably  best  explained  by  the  mode  of 
infection.  It  is  known  that  the  malarial  mosquitoes  feed  almost 
solely  at  night  and  usually  only  once  during  the  night.  If  a 
subject  is  inoculated  by  the  mosquito  on  two  successive  nights 
it  is  obvious  that  the  parasite  would  become  mature  with  an 
interval  of  about  twenty-four  hours  between  the  generations. 
If  inoculation  should  occur  upon  three  or  more  successive  nights 
it  is  probable  that  the  third  and  succeeding  generations  would 
sporulate,  after  incubation,  simultaneously  with  the  first  and 
second.  The  interval  between  multiple  quartan  infections 
may  be  explained  similarly. 

Latency  and  relapses  were  formerly  explained  upon  the  theory 
that  so  long -as  the  parasites  remained  below  a  certain  level 
of  asexual  reproduction  the  disease  was  latent,  and  when  the 
parasites  exceeded  in  number  this  level  a  relapse  occurred. 
Sims  has  estimated  the  greatest  number  of  adult  parasites  which 
the  body  can  endure  without  symptoms  as  about  two  billions. 
It  is  probable  that  brief  periods  of  latency  may  be  thus  explained, 
especially  in  persons  possessing  a  relative  immunity,  but  it  is 
evident  that  this  is  not  a  common  mode,  particularly  of  relapses 
at  long  intervals,  since  the  asexual  cycle  is  known  to  wear  out 
spontaneously  after  certain  periods.  These  relapses  at  long 
intervals  can  be  explained  by  parthenogenesis  alone.  After  the 
schizonts  have  perished,  while  the  microgametocytes  do  not 
persist  long,  the  macrogametes  remain  for  indefinite  periods. 
Th'ey  may  sporulate  more  or  less  regularly,  causing  paroxysms 
at  intervals  of  about  a  week,  or  multiples  thereof,  or  may  lie 
dormant  until  aroused  into  reproductive  activity  by  exposure  or 
dietary  or  other  excesses.  It  is  highly  probable  that  the 
parthenogenetic  cycle  of  reproduction  is  conducted  almost 
altogether  in  the  visceral  circulation,  particularly  in  the  spleen. 


As  evidence  of  this  may  be  cited  the  outbreaks  of  malaria  follow- 
ing cold  douching,  electrical  stimulation,  and  trauma  of  the 
splenic  region. 

The  anemia  of  malaria  depends  upon  three  factors:  (i)  The 
mechanical  destruction  of  cells  by  the  parasites;  (2)  the  effect 
of  toxins;  and  (3)  the  activity  of  the  blood-making  organs. 
Liberated  hemoglobin  is  transformed  by  the  liver  into  bile 
pigment.  When  the  hemoglobin  is  liberated  too  fast  for  the 
liver  to  utilize,  hemoglobinemia  results,  and  hemosiderin  is 
precipitated  from  the  blood.  The  increased  activity  of  the 
liver  results  in  polycholia  and  icterus.  It  is  probable  that 
jaundice  is  due  also,  when  the  liver  capacity  is  overtaxed,  to 
hemoglobinemia.  When  hemoglobinemia  exceeds  a  certain 
limit  the  hemoglobin  is  excreted  by  the  kidneys,  resulting  in 
hemoglobinuria. 

Splenic  enlargement  is  effected  through  hyperemia,  deposition 
of  detritus  of  destroyed  erythrocytes,  accumulation  of  para- 
sites, and  hyperplasia  of  the  pulp. 

Spontaneous  cure  is  probably  due  to  the  natural  weakening 
of  the  reproductive  powers  of  the  parasite,  a  phenomenon  occur- 
ring in  strains  throughout  the  vegetable  and  animal  kingdoms, 
and  possibly  also  to  the  influence  of  an  antitoxin.  Phagocy- 
tosis plays,  in  my  opinion,  a  much  less  prominent  role  than  is 
usually  attributed  to  it.  It  is  probable  that  this  function  is 
exercised  mainly  after  the  parasites  have  lost  vitality  from 
other  causes. 

ETIOLOGY  OF  PERNICIOUS  MALARIA 

Pernicious  malaria  is  almost  as  varied  in  pathogenesis  as 
it  is  in  manifestations.  Not  only  are  its  several  forms  asso- 
ciated with  unlike  conditions,  but  for  the  explanation  of  some 
the  presence  of  several  different  factors  is  necessary.  Thus 
comatose  malaria  may  be  associated  with  at  least  two  different 
forms  of  the  parasite;  the  peripheral  blood  may  show  very  great 
numbers  of  these  parasites  or  they  may  be  scanty;  in  the 
brain  they  may  be  found  in  hordes,  even  to  the  occlusion  of 
small  vessels,  or  they  may  be  entirely  absent. 


ab  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

As  may  be  inferred,  no  one  etiologic  element  can  account 
for  all  cases,  even  of  the  same  type.  Probably  the  only  es- 
sential common  factor  is  the  presence  of  the  malarial  parasite, 
the  manifestations  of  which  run  the  gamut  from  the  mildest 
intermittent  to  the  profoundest  cachexia,  from  the  most 
artfully  masked  to  the  deadliest  pernicious. 

Until  comparatively  recently  it  was  believed  that  infections 
with  the  so-called  benign  organisms  never  gave  rise  to  pernicious 
symptoms.  I  have,  however,  collected^*''  a  number  of  cases 
in  which  these  organisms  were  responsible  for  pernicious  attacks. 

Pernicious  symptoms  occur  more  rarely  in  connection  with 
the  quartan  infections  than  with  simple  tertian.  The  reasons 
for  this  are  probably  the  relative  rarity  of  quartan  fever  and 
the  more  even  distribution  of  parasites  throughout  the  circula- 
tion, there  being  slight  tendency  to  form  accumulatio  s. 

It  is  not  yet  known  with  certainty  which  variety  of  the 
estivo-autumnal  parasite  gives  rise  most  frequently  to  per- 
niciousness.  That  the  crescentic  form  of  the  parasite  has  an 
intimate  relation  to  the  production  of  the  pernicious  fevers 
is  improbable,  for  the  following  reasons:  First,  crescents  alone 
may  be  found  in  the  peripheral  blood,  and  intense  localization 
of  active  forms  be  present  in  the  brain  or  other  viscera.  The 
number  of  parasites  in  the  superficial  circulation  is  not  a 
reliable  guide  to  the  severity  of  the  attack.  Of  Ewing's  64 
cerebral  cases  no  parasites  were  identified  in  11,  and  in  many  of 
his  33  cases  in  which  crescents  alone  were  found  the  search  was 
successful  only  after  one  and  two  hours.  Second,  crescents 
are  rarely,  if  ever,  present  in  the  parasitic  localizations  and 
thrombi  are  frequently  observed  in  pernicious  cases. 

Of  the  pathogenic  factors  which  excite  perniciousness  the 
following  are  to  be  regarded  as  the  most  important  and  approxi- 
mately of  relatively  equal  importance: 

1.  An  excessive  number  of  parasites. 

2.  Localizations  of  parasites. 

3.  Toxins. 

4.  Individual  predisposition  and  external  etiologic  influences. 
Number  of  Parasites. — Golgi's  law,  that  the  number  of  para- 
sites determines  the  severity  of  the  attack,  has  been  generally 


MALARIA  87 

accepted.  Cases  in  which  the  parasites  are  in  very  great 
numbers  in  the  peripheral  blood  are  usually  accompanied  by 
coma.  That  the  parasites  are  abundant,  either  absolutely 
in  the  body  as  a  whole  or  relatively  in  certain  areas,  probably 
holds  good  in  a  great  majority  of  the  cases,  though  we  cannot 
always  attribute  perniciousness  to  the  large  number  of  parasitic 
forms.  I  have  observed  one  case  of  severe  comatose  malaria 
in  a  boy,  aged  twelve,  in  whose  peripheral  blood  the  parasites 
were  scanty. 

On  the  other  hand,  the  superficial  circulation  may  be  teeming 
with  parasites,  while  the  patient  experiences  only  a  mild  attack. 
Thus  A.  Plehn'*  gives  the  histories  of  two  cases  in  which  the 
symptoms  were  slight  though  the  peripheral  blood  showed  as 
many  as  thirty-five  and  forty-six  tropic  parasites,  respectively, 
to  each  field  of  the  microscope. 

It  is  highly  probable  that  an  enormous  number  of  parasites, 
equally  distributed,  depend  for  their  power  to  elicit  pernicious 
symptoms  upon  the  increased  quantity  of  toxin  elaborated. 

Localizations  of  Parasites. — Accumulations  of  parasites  in 
the  brain  were  first  described  by  Planer  (1845)  ^.nd  by  Frerichs 
(1861);  those  in  the  liver  by  Guarnieri  (1867).  Localizations 
in  the  brain  have  been  found  associated  with  a  wide  variety  of 
cerebral  symptoms:  in  the  mucosa  of  the  alimentary  tract, 
with  gastro-intestinal  symptoms  and  typical  algid  attacks; 
in  the  heart,  with  cardiac  symptoms;  in  the  medulla,  with 
bulbar  paralysis;  in  the  retina,  with  amblyopia;  in  the  pancreas, 
with  hemorrhagic  pancreatitis,  etc.  In  proportion  to  the 
amount  of  damage  sustained  by  the  kidneys  in  malaria  there 
is  less  tendency  for  parasites  in  pernicious  attacks  to  accumulate 
in  these  organs  than  in  any  other  of  the  body. 

These  localizations  consist,  in  the  main,  of  parasite-infected 
red  blood-cells.  There  may  be,  however,  pigmented  leucocytes 
and  free  parasites  and  pigment.  The  parasites  in  each  par- 
ticular case  may  be  of  the  same  or  of  different  stages  of  develop- 
ment. The  pigmented  and  sporulating  forms  are  probably 
oftenest  seen,  but  the  earlier  phases  are  frequently  observed. 
It  would  seem  reasonable  that  the  crescents,  on  account  of  their 
size,  would  frequently  form  an  important  element  in  these 


88  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

accumulations  of  parasites,  but  such  does  not  appear  to  be  the 
case. 

The  symptoms  present  in  cases  in  which,  on  post-mortem 
examination,  localization  of  parasites  are  demonstrated  are  not 
always  referable  to  these  aggregations  alone,  since  changes  are 
frequently  observed  which  are  secondary  to  parasitic  throm- 
bosis, and  may  outweigh  the  latter  in  pathogenic  importance. 

The  most  conspicuous  of  these  changes  are  perivascular 
exudation,  hemorrhage,  and  necrosis.  The  hemorrhages  are 
usually  punctate. 

This  propensity  of  the  parasites  in  pernicious  fever  to  con- 
gregate undoubtedly  explains  the  course  of  many  cases,  but 
by  no  means  all.  Fatal  cases  of  comatose  malaria  have  been 
observed  with  no  parasites  at  all  in  the  brain.  It  is  not  known 
whether  parasitic  thrombi  may  exist  without  producing 
symptoms. 

Toxins. — The  evidence  of  the  existence  of  a  toxin  in  malaria 
has  been  detailed  above. 

Individual  Predisposition  and  External  Etiologic  Influences. 
— These  influences,  in  many  instances,  doubtless  not  only 
induce  the  attack  but  determine  its  type.  Organs  or  systems 
enfeebled  by  antecedent  ailments  are  apt  to  play  the  title  role 
in  the  pernicious  tragedy.  Thus  algid  and  choleraic  attacks 
may  be  associated  with  a  history  of  intestinal  catarrh;  the 
comatose  and  delirious  cases,  with  a  history  of  abuse  of  alcohol; 
the  convulsive,  with  epilepsy,  etc.  It  is  not  improbable  that 
some  cases  of  dysenteric,  cardialgic,  syncopal,  tetanic,  cataleptic, 
paralytic,  pneumonic,  pleuritic,  gastralgic,  and  other  forms 
described  by  the  older  writers  may  be  similarly  explained. 

Malarial  subjects  who  are  much  exposed  to  the  heat  of  the 
sun  are  liable  to  be  stricken  with  pernicious  fever,  especially 
of  the  cerebral  type.  This  danger  is  enhanced  if  to  the  solar 
heat  are  added  fatigue,  deficient  or  improper  food,  or  other 
hardships.     Certain  psychic  states  have  causative  significance. 

In  addition  to  the  four  principal  factors  enumerated,  con- 
gestion of  viscera  and  parasitic  obstruction  of  the  hepatic 
capillaries  have  been  regarded  as  important.  It  is  probable 
that  they  have  little  influence. 


A  feeble  phagocytic  activity  was  considered  by  Golgi  as 
predisposing  to  pernicious  attacks.  In  the  present  state  of 
our  knowledge  it  is  impossible  to  define  the  relation  of  this 
function  to  perniciousness. 

A  consideration  of  the  relative  frequency  with  which  the 
several  factors  are  concerned  in  the  pathogenesis  of  the  various 
forms  of  pernicious  malaria  will  necessarily  be  brief.  In  the 
comatose  variety  any  of  the  four  chief  agents  may  take  part; 
idiosyncrasy  and  external  influences  may  unite  with  any  of 
the  other  factors;  an  extraordinary  number  of  parasites  in  the 
general  circulation,  without  accumulations  in  the  brain,  is 
productive  of  coma  probably  because  of  the  toxin. 


CHAPTER  III 

PATHOLOGIC  ANATOMY  OF  MALARIA 

ACUTE  MALARIA 

Intravascular  melanin,  which  is  a  product  of  hemoglobin 
converted  through  the  biologic  agency  of  the  malarial  parasites, 
is  the  pathognomonic  anatomic  feature  of  malaria.  Melanin 
occurs  in  the  tissues  also,  but  here  there  is  some  doubt  as  to 
its  origin.  It  is  brownish  black  in  color,  occurs  in  fine  grains, 
coarse  particles,  or  in  .lumps;  does  not  yield  the  reaction  for 
iron,  and  is  insoluble  in  acids,  but  is  readily  dissolved  by  am- 
monium sulphide.  This  should  not  be  confused  with  hemo- 
siderin, which  is  a  chemic  derivation  of  the  hemoglobin  of 
broken-down  red  blood-cells;  is  yellowish  in  color;  responds  to 
the  reaction  for  iron;  is  insoluble  in  acids,  alkalies,  alcohol  and 
water;  and  exists  especially  extravascularly.  It  is  regarded 
as  a  result  of  prolonged  hemoglobinemia  following  severe  or 
chronic  infections. 

The  general  plan  of  distribution  of  melanin  may  be  thus  stated : 
In  the  blood  current  it  may  exist  free  or,  more  commonly,  is 
contained  within  the  phagocytes  and  the  red  cells  infected 
with  pigmented  parasites,  and  is  more  abundant  in  the  capil- 
laries than  in  the  larger  vessels.  In  the  viscera  it  is  oftenest 
seen  in  the  spleen,  bone-marrow,  brain,  and  liver,  especially 
in  the  endothelial  cells,  but  in  the  spleen  and  bone-marrow  it 
exists  also  outside  the  vessels  and  either  between  or  within  the 
cells  proper  to  these  tissues. 

The  distribution  of  the  parasites  varies  according  to  the  type 
of  the  attack;  it  has  been  shown  that  the  latter  depends  largely 
upon  the  localizations  of  the  parasites.  They  are  usually 
abundant  in  the  splenic  blood  irrespective  of  the  form  assumed 
by  the  attack.  It  occasionally  happens  that  death  supervenes, 
notwithstanding  a  progressive  diminution  of  the  parasites, 
so  that  the  latter  may  be  scanty  or  even  absent.     In  the  spleen 


MALARIA  gi 

are  found  not  only  schizonts,  but  also  numerous  sexual  forms, 
which  are  likewise  usually  found  in  the  bone-marrow  and  even 
in  the  liver,  but  in  the  brain  gametes  are  conspicuously  few. 
Parasitic  development  is  checked  almost  immediately  upon  the 
death  of  the  host. 

The  spleen  is  always  more  or  less  enlarged,  though  perhaps 
slightly  so  in  acute  cases  following  recent  infection.  The  edges 
are  often  rounded,  the  organ  tending  to  lose  its  characteristic 
contour  and  to  assume  a  spheric  shape.  The  color  varies  from 
reddish  brown  to  almost  black,  being  darker  in  old  malarials. 
In  consistence  it  is  usually  softer  than  normal,  often  semifluid, 
sometimes  resembling  a  bag  of  pulp.  The  capsule  is  thinned, 
occasionally  adherent  to  the  adjacent  organs,  and  is  very  liable 
to  rupture.  The  cut  surface  is  dark  in  proportion  to  the  age 
of  the  infection.  The  pigmentation  is  occasionally  uniform 
and  the  tissue  hardly  distinguishable,  though,  as  a  rule,  the 
Malpighian  bodies  stand  out  distinctly.  The  venous  sinuses 
are  often  dilated.  Microscopically  there  is  enormous  cellular 
hyperplasia  with  distention  of  Mall's  pulp  cords.  The  spleen 
cells  are  everywhere  intercalated  with  red  blood  corpuscles,  a 
large  per  cent,  of  which  are  infected.  The  parasites  may  be 
in  the  same  or  in  different  stages  of  development.  The  pig- 
ment is  contained  in  the  large  mononucleated  leucocytes, 
endothelial  cells,  and  giant  cells.  The  latter  contain  also  red 
cells,  parasites,  and  even  small  phagocytes,  and  are  most  abun- 
dant in  the  splenic  vein.  They  sometimes  show  evidences  of 
necrosis.  The  Malpighian  bodies  and  the  fibrous  trabeculse 
are  usually  unpigmented.  Mitotic  cells  may  be  found  in  the 
pulp  and  in  the  Malpighian  bodies.  The  circulation  may  be 
so  obstructed  that  edema,  interstitial  hemorrhage,  and  cellular 
necrosis  may  occur. 

The  liver  is  generally  enlarged,  but  in  a  less  proportion  as  to 
frequency  and  size  than  the  spleen.  The  color  is  usually  a  dirty 
brown,  the  surface  is  sleek,  and  the  form  is  preserved.  The 
consistence  may  be  normal  or  somewhat  diminished.  The 
parenchyma  presents  a  reddish-brown  color  after  recent  in- 
fection and  the  cut  surface  drips  blood.  The  gall-bladder  is 
often   distended   with  a   quantity   of   dark,   inspissated   bile. 


92  ENDEMIC    DISEASES    OF    THE    SOUTHEEN    STATES 

Microscopically  parasites  are  not  so  abundant  as  in  the  spleen. 
Pigment  is  found  in  the  vessels,  especially  in  the  blood  capillaries. 
Here  are  found  also  altered  parasites,  melaniferous  leucocytes, 
and  large  endothelial  cells  containing  coarse  grains  of  pigment. 
The  macrophages  are  sometimes  of  an  enormous  size.  The 
pigmented  endotheHal  cells  are  swollen  and  the  capillaries  are 
not  infrequently  entirely  obstructed  with  pigmented  cellular 
elements.  The  hepatic  cells  do  not  contain  melanin,  but  are 
frequently  charged  with  hemosiderin,  and  may  show  evidences 
of  cloudy  swelling,  atrophy,  or  necrosis.  Karyokinesis  is 
occasionally  noted.    Areas  of  focal  necrosis  have  been  described. 

The  kidneys  on  gross  inspection  show  few  changes ;  they  may 
be  slightly  enlarged  and  hyperemic.  Microscopic  examination 
shows  a  marked  pigmentation  of  the  Malpighian  corpuscles, 
together  with  degenerated  tubular  epithelium.  While  the 
epithelium  of  the  tubules  may  be  healthy,  it  often  shows  cloudy 
swelHng  and  necrosis.  In  the  straight  tubules  there  may  be 
casts  of  various  sorts.  Melanin  is  found  in  the  glomeruli, 
less  often  in  the  tubules.  The  cells  may  contain  hemosiderin 
granules.  Parasites  are  rare  in  the  glomerular  vessels,  but 
may  be  found  in  the  intertubular  capillaries.  Ewing's^"^  case 
with  massing  of  the  parasites  in  the  renal  capillaries  has  been 
mentioned.  A  true  glomerulitis  has  been  found  in  cases  of 
Ihe  algid  type. 

In  cerebral  cases  the  only  variation  from  the  normal  condi- 
tion of  the  stomach  and  bowels  may  be  a  slight  pigmentation. 
In  fatal  cases  of  the  algid  and  choleraic  forms  the  gastro- 
intestinal tract  may  contain  a  bloody  fluid  and  the  mucous 
membrane  may  be  swollen,  hyperemic,  pigmented,  necrotic  or 
ulcerated.  The  follicles  and  Peyer's  patches  may  be  hyper- 
trophied  and  prominent.  Microscopically  there  is  vivid  in- 
jection, parasitic  and  pigmentary  thrombosis  of  the  capillaries, 
hemorrhagic  points,  and  necrosis.  The  peritoneum  is  usually 
normal. 

Macroscopically  the  lungs  may  show  nothing  abnormal  save, 
probably,  slight  results  of  hypostasis,  which  in  some  cases  may 
be  cadaveric  lesions.  Occasionally  there  are  hemorrhagic 
areas.     Microscopically  neither  pigment  nor  parasites  are  so 


MALARIA  93 

evident  as  in  certain  of  the  other  organs.  The  capillaries  are 
congested,  sometimes  thrombosed,  and  contain  infected  ery- 
throcytes, phagocytes,  which  often  show  signs  of  degeneration, 
and  macrophages.  The  capillary  epithelium  may  be  swollen, 
but  is  only  occasionally  pigmented.  The  pleura  show  nothing 
abnormal. 

The  heart  muscle  is  ordinarily  pale  and  flabby,  but  the 
muscular  fibers  do  not  usually  afi'ord  degenerative  signs.  The 
capillaries  may  contain  parasites  in  greater  or  less  number,  and 
the  endothehum  may  be  swollen.  Cases  in  which  the  parasites 
are  very  numerous  in  the  cardiac  capillaries,  such  as  that  of 
Ewing,^^*  are  very  rare. 

In  cerebral  cases  the  meninges  of  the  brain  are  deeply 
hyperemic,  and  excess  of  serum  is  found  in  the  meshes  of  the 
pia,  in  the  ventricles,  and  at  the  base  of  the  brain.  The 
cerebral  substance  is  commonly  darkly  pigmented  and  con- 
gested, and  may  show  hemorrhages,  usually  punctiform, 
occasionally  larger.  The  hemorrhages  occur  oftener  in  the 
cerebrum,  but  may  be  present  in  the  cerebellum.  In  the 
abdominal  form  the  brain  may  show  but  few  pathologic  changes. 
Microscopically  in  the  cerebral  cases  the  capillaries  are  seen 
to  be  filled,  even  to  occlusion,  with  pigment,  parasites,  and 
phagocytes,  the  later  in  the  same  or  in  dift'erent  stages  of 
schizogony;  gametes  are  seldom  found.  In  some  instances 
nearly  every  red  cell  contains  one  or  more  parasites.  Localiza- 
tion of  parasites  are  found  not  only  in  the  cerebrum,  but  also 
in  the  cerebellum  and  medulla.  The  capillary  endothelium 
may  be  swollen,  pigmented,  and  undergoing  fatty  degeneration. 
Secondary  changes,  such  as  perivascular  exudation,  hemor- 
rhages, and  necrosis,  are  not  uncommon  results  of  thrombosis. 
Degenerative  changes  in  the  ganglion  cells  have  been  detected. 

The  bone-marrow  is  of  a  dark  color  approaching  that  of  the 
spleen,  and  sometimes  diffluent.  Microscopic  examination 
reveals  hyperemia,  the  capillaries  being  engorged  with  pig- 
mented parasites  and  giant  cells  clinging  to  the  vessel  walls. 
The  parasites  exist  as  free  spores,  schizonts,  which  are  fre- 
quently sporulating,  and  gametes  in  large  numbers.  Extra- 
vascular  parasites  and  free  pigment  are  also  found. 


94  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

CHRONIC  MALARIA 

The  spleen  is  always  enlarged.  The  form  is  usually  pre- 
served. Its  average  weight  is  from  700  to  800  grams,  though 
it  may  attain  four  or  five  times  this  weight.  In  consistence 
it  is  usually  firmer  than  normal.  The  capsule  is  thickened, 
especially  at  the  convexity.  Upon  the  surface  are  scattered 
indurated  whitish  plaques  of  fibrous,  occasionally  of  calcareous 
consistence,  evidences  of  perisplenitis.  Adhesions  to  the  dia- 
phragm or  other  parts  are  not  infrequent.  Subcapsular  in- 
farcts are  occasionally  encountered.  In  section  the  parenchyma 
is  usually  found  firm;  only  rarely  is  it  of  diminished  consistence. 
The  color  varies  from  that  of  muscular  tissue  to  slate  color. 
The  thickened  trabecular,  like  white  bands,  are  very  evident. 
The  Malpighian  follicles  are  sometimes  conspicuous,  sometimes 
indistinct.  In  old  cases  there  is  an  overgrowth  of  connective 
tissue,  particularly  near  the  capsule.  Histologically  the  chief 
changes  found  are  trabecular  hyperplasia  and  venous  dilatation. 
The  process  sometimes  resembles  a  hypertrophic  cirrhosis. 
The  fibrous  trabecule  are  hypertrophied  and  there  is  formation 
of  new  connective  tissue.  The  venules  are  notably  dilated, 
the  walls  thickened,  and  the  blood  rich  in  pigmented  leucocytes 
and  macrophages.  The  deposition  of  pigment  is  in  general 
similar  to  that  in  acute  malaria.  There  is  at  times  little  change 
in  the  lymphoid  tissue  forming  the  arterial  sheaths  and  Mal- 
pighian bodies,  but  this  may  be  hyperplastic.  Necrosis  of  the 
spleen  pulp  -is  observed,  surrounded  by  evidences  of  regenera- 
tion. These  regenerative  processes  consist  chiefly  of  increased 
vascularization,  formation  of  connective-tissue  network  en- 
closing giant  cells,  and  hyperplasia  of  lymphoid  tissue  beginning 
in  the  Malpighian  bodies. 

The  liver  is  not  so  constantly  enlarged  as  is  the  spleen  and 
never  attains  so  excessive  a  degree  of  hypertrophy.  It  may 
weigh  from  2  to  4  kg.  In  rare  instances  it  is  atrophic. 
The  consistence  is  firm,  occasionally  somewhat  doughy.  The 
capsule  is  tense  and  may  be  thickened.  There  may  be  present 
whitish  bands  or  patches,  the  results  of  perihepatitis.  The 
color  varies  from  reddish  to  almost  black.     The  cut  surface 


MALARIA  95 

is  usually  found  to  be  congested  and  may  drip  with  blood. 
The  color  is  more  or  less  dark  red.  There  may  sometimes  be 
detected  on  gross  inspection  an  increase  of  connective  tissue. 
Microscopically  the  hepatic  cells  are  seen  to  be  hypertrophied 
and  hyperplastic,  showing  evidences  of  cloudy  swelhng  and 
necrosis,  or  atropliied  as  a  consequence  of  vascular  dilatation. 
In  certain  areas  there  may  be  a  complete  disappearance  of 
hepatic  cells  which  are  replaced  by  connective  tissue,  Kupffer's 
cells,  or  beginning  formation  of  new  hepatic  cells.  The  nuclei 
are  frequently  multiple,  and  when  single  may  be  much  larger 
than  normal  and  contain  one  to  two  nucleoli.  The  hepafic 
cells  may  be  charged  with  hemosiderin.  Pigment  is  contained 
in  the  endothelial  and  Kupffer's  cells,  especially  in  congested 
areas  and  in  the  periphery  of  the  lobule.  There  is  sometimes 
diffuse  overgrowth  of  connective  tissue.  The  blood  capillaries 
are  usually  dilated  and  congested  with  blood  rich  in  pigmented 
leucocytes;  the  circulation  is  commonly  sluggish.  The  bile 
capillaries  are  ordinarily  unaltered.  The  perivascular  lymph 
channels  may  be  dilated.  Amyloid  degeneration,  beginning 
apparently  at  the  periphery  of  the  lobules,  is  not  rare. 

The  kidneys  are  usually  increased  in  volume  and  in  weight. 
The  contracted  kidney  has  been  described  in  connection  with 
malaria,  but  there  is  some  doubt  as  to  the  etiologic  relationship. 
The  surface  of  the  kidney  is  smooth,  the  color  is  dark  red,  and 
the  consistence  is  sUghtly  increased.  Upon  section  the  cortical 
substance  is  reddish  gray.  The  pyramids  are  markedly  hyper- 
emic,  the  red  tint  being  most  decided  at  the  border  of  the 
pyramidal  substance.  Upon  microscopic  examination  the 
convoluted  tubules  and  ascending  limb  of  Henle's  loop  are 
found  dilated.  The  epithelium  is  swollen,  charged  with 
hemosiderin,  and  may  be  undergoing  degeneration.  In  the 
collecting  tubules  the  epithehum  is,  as  a  rule,  only  slightly 
altered.  These  tubules  rarely  contain  granular  or  hyaline 
casts  or  desquamated  epithelium.  Bowman's  capsule  presents 
changes  similar  to  those  of  the  convoluted  tubules.  The 
renal  arterioles  are  congested  and  the  capillaries  are  dilated 
and  gorged  with  blood  rich  in  leucocytes,  more  marked  in  the 
pyramidal  than  in  the  cortical  substance.     Malanemia  is  not 


g6  ENDEMIC   DISEASES    OF   THE    SOUTHERN   STATES 

SO  decided  in  the  kidney  even  when  profuse  in  the  spleen  and 
liver.  There  is  generally  little  change  in  the  connective  tissue. 
Here  and  there  is  a  shght  thickening  of  the  intertubular  con- 
nective tissue.  The  blood-vessels,  the  glomeruH,  and  the  walls 
of  the  renal  tubules  may  undergo  amyloid  degeneration.  This 
is  more  diffuse  in  the  kidneys  in  chronic  malaria  than  in  the 
other  organs. 

The  alimentary  tract  may  show  evidence  of  amyloid  degenera- 
tion in  the  stomach  or  bowel  and  dysenteric  lesions  in  the 
colon. 

In  the  lungs  may  be  pigmentation  and  anemia,  and  in  the 
pleural  cavity  an  effusion. 

The  heart  is  relaxed  and  often  dilated  and  sometimes  shows 
evidence  of  degeneration  of  the  musculature. 

The  bone-marrow  is  of  firmer  consistence  and  more  deeply 
colored  than  normal,  especially  toward  the  ends  of  the  long 
bones.  There  is  usually  a  decrease  of  fat  and  a  proliferation 
of  marrow  cells,  together  with  large  cells,  some  undergoing 
karyokinesis,  lymphoid  cells,  and  nucleated  red  cells.  The 
vessel  walls  are  thickened.  In  some  instances  there  is  atrophy 
of  the  bone-marrow. 

The  elimination  of  the  pigment  probably  consumes  three  or 
four  months  after  the  cessation  of  infection,  though  this  varies 
with  the  activity  of  the  eliminative  process. 


CHAPTER  IV 
CLINICAL  HISTORY  OF  MALARIA 

ACUTE  MALARIA 

Incubation. —  The  period  of  incubation  varies  within  very 
wide  limits.  It  may  be  stated  as  a  general  proposition  that  the 
incubation  period  is  longest  in  quartan  infections  and  shortest 
in  the  estivo-autumnal.  The  average  period  is,  for  quartan, 
twelve  to  eighteen  days;  tertian,  six  to  fourteen  days,  and  estivo- 
autumnal,  two  to  ten  days.  Much  longer  periods  running 
into  several  months,  have  been  reliably  recorded.  These  must 
be  regarded  as  cases  of  chronic  malaria  where  the  latent  stage 
precedes  the  active,  and  are  analogous  to  those  cases  of  syphilis 
in  which  the  secondary  manifestations  occur  without  recognized 
primary  lesion,  and  are  to  be  explained  satisfactorily  only  by 
parthenogenesis. 

General  Description  of  a  Malarial  Paroxysm. — The  forms 
of  acute  malaria  have  so  many  points  in  common  that  it  is 
convenient  to  describe  first  the  typic  malarial  paroxysm. 

Prodromata  may  be  perceived  by  the  patient.  They  may 
correspond  to  the  last  few  parasitic  sporulations  preceding 
that  which  causes  the  paroxysms,  or  may  occur  only  a  few  hours 
before  the  access.  They  are  ill-defined,  but  usually  consist 
of  languor,  anorexia,  headache,  aching  of  the  loins  and  hips, 
thirst,  epigastric  distress,  a  disposition  to  stretch  and  yawn, 
and  chilHness  along  the  course  of  the  spine.  These  symptoms 
may  be  so  shght  as  to  escape  attention.  The  typic  malarial 
paroxysm  comprises  three  well-marked  stages:  the  cold  stage, 
the  hot  stage,  and  the  sweating  stage. 

The  cold  stage  presents  itself  with  the  rapid  intensification 
of  the  prodromata  described.  The  sensation  of  coldness  spreads 
to  every  part  of  the  body.  The  skin  becomes  pale,  especially 
the  lips  and  the  ears,  as  well  as  the  nails,  and  the  papillae  of  the 
skin  stand  out,  forming  the  so-called  "goose-skin."  The 
patient  shivers,  sometimes  so  violently  that  he  shakes  the  bed; 

7  97 


gS  ENDEMIC   DISEASES    OF    THE    SOUTHERN    STATES 

he  covers  up,  his  teeth  chatter,  and  he  looks  and  feels  cold. 
The  slightest  motion  of  the  body  or  of  the  bedclothing  increases 
the  vehemence  of  these  phenomena.  Notwithstanding  these 
evidences  of  coldness,  the  thermometer  shows  an  elevation  of 
internal  temperature.  The  fever  may  even  precede  the 
cold  stage.  The  patient  complains  of  a  tight  headache,  a 
backache,  precordial  oppression,  and  dyspnea.  He  often 
complains  of  general  soreness,  as  severe  as  if  having  been  beaten. 
He  may  suffer  with  nausea  and  vomiting  of  bile.  There  is  apt 
to  be  frequent  micturition  of  small  quantities  of  limpid  urine. 
The  respiration  is  rapid  and  tremulous.  The  pulse  is  ac- 
celerated, diminished  in  volume,  and  increased  in  tension. 
The  cold  stage  may  last  from  a  few  minutes  to  two  or  three 
hours. 

With  the  onset  of  the  hot  stage  hot  flashes  alternate  with  cold 
until  the  sense  of  heat  becoming  general,  the  patient  presents  a 
very  different  picture  from  that  of  the  first  stage.  He  begins 
to  uncover,  the  skin  is  flushed  and  hot,  the  pulse  full  and 
bounding,  the  respiration  deeper,  and  the  urine  is  scanty 
and  high  colored.  There  may  be  constipation  or  diarrhea. 
The  tongue  is  coated,  bulky,  and  usually  shows  indentations 
produced  by  the  teeth.  Herpes  appears  upon  the  lips  or  nose. 
The  spleen  is  enlarged  and  the  upper  half  of  the  abdomen  is 
tender  on  pressure.  The  headache,  soreness,  nausea,  and 
vomiting  continue,  there  is  often  great  thirst  and  epigastric 
pain,  and  the  temperature  continues  to  rise. 

When  the  temperature  is  at  its  height  the  sweating  stage  is 
ushered  in  by  crisis.  Beads  of  perspiration  begin  to  appear 
upon  the  face,  then  a  universal  sweat  breaks  out,  and  the  skin, 
which  was  first  cold  and  rough,  then  hot  and  dry,  now  becomes 
moist  and  natural.  The  temperature  falls  to  normal,  often  a 
little  below;  the  pulse  and  respiration  resume  their  normal 
features.  The  soreness  disappears,  the  thirst  ceases,  and  the 
patient  often  feels  so  comfortable  that  he  takes  a  short  nap. 

Such  is  the  typic  procession  of  one  of  the  most  remarkable 
events  in  the  category  of  disease.  The  conspicuous  changes, 
the  swift  succession  of  stages,  and  the  punctual  periodicity  of 
paroxysms  are  unparalleled  in  pathology. 


MALARIA 


99 


In  some  paroxysms,  however,  one  or  two  stages  may  be 
missing.  The  temperature  may  rise  unaccompanied  by  a 
cold  stage  or  may  fall  to  normal  unattended  by  sweats.  This 
constitutes  the  so-called  dumb  chill.  The  cold  stage  is  the 
least  constant,  the  hot  stage  the  most  so.  The  cold  stage  is 
most  constant  in  quartan  fever,  least  so  in  estivo-autumnal 
infections. 

Simple  Tertian  Infection. — Infection  with  a  single  brood 
of  simple  tertian  parasites  causes  a  paroxysm  every  other  day. 


Of 

Q. 
UJ 

300 
290 
280 
270 
260 
250 
240 
230 
220 
210 
200 
190 
180 
170 

DAY  OF 
DISEASE 

n 

DAY  OF 

HOUR. 

:eNT. 
41»— 

400— 

39°- 

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37»— 

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102° 
101° 
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99» 
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Fig.   25. — Single  tertian  infection. 

That  the  parasites  are  in  the  same  stage  of  development,  causes 
great  regularity  in  the  course.  From  the  beginning  of  one 
paroxysm  to  the  beginning  of  another  is  almost  precisely  forty- 
eight  hours.  When  the  interval  is  not  quite  so  long,  as  some- 
times happens,  the  paroxysms  are  said  to  anticipate;  when 
longer,  as  is  more  rarely  the  case,  they  are  said  to  postpone  or 
to  retard.  Postponing  is  usually  regarded  as  evidence  of  abating 
activity. 

In  more  than  half  the  simple  tertian  cases  the  infection  is 
double;  that  is,  there  are  two  distinct  generations  of  parasites. 
These  generally  mature  on  alternate  days,  two  paroxysms  on 


lOO  EXDEinC    DISEASES    OF    THE    SOX'THEEX    STATES 

one  day  with  an  intervening  day  of  apyrexia  being  extremely 
rare.  The  paroxysms  may  occur  at  the  same  time  ever}"  day 
and  be  similar  in  every  respect.  Usually,  however,  there  is  a 
perceptible  difference  between  the  paroxysms  of  successive 
days,  a  difference  consisting  of  time  of  onset,  severity,  and 
relative  length  of  the  stages  of  the  parox^'sms.  It  very  rarely 
happens  that  the  paroxysms  are  so  lengthened,  and  one  so 
anticipates  that  its  onset  occurs  during  the  latter  stage  of  the 
preceding  paroxysm.     They  are  styled  subintrant  attacks. 


300 
290 
250 
270 
260 
250 
2-10 
230 

210 
200 
190 
180 
170 
160 

DAY  OF 

DISEASE 

SlO^Sf 

HOLR. 

41«— 
40»— 
39»- 

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102° 
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96° 

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Fis.  20. — Double  tertian  infection. 


A  change  of  t3"pe  from  quotidian  to  tertian  paroxysms,  or 
vice  versa,  is  commonly  obser^•ed.  The  change  from  quotidian 
to  tertian  may  be  spontaneous  or  the  result  of  incomplete 
medication  or  improvement  in  hygienic  conditions,  one  group  of 
parasites  perishing.  A  change  from  tertian  to  quotidian  may 
occur  without  apparent  cause  or  follo'n'ing  indiscretions  of 
various  sorts. 

The  onset  is  probably  more  common  during  the  morning, 
but  this  is  neither  constant  nor  of  diagnostic  dignity.  The 
invasion  is  almost  always  -nath  a  chill.  The  temperature  rises 
suddenlv  and  falls  likewise.     Commonlv  there  are  no  grave 


symptoms,  but  a  mild  delirium  is  not  rare.  The  temperature 
usually  goes  as  high  as  103°  to  io5°F.  The  average  duration 
of  the  paroxysm  is  from  eight  to  twelve  hours. 

During  apyrexia  the  patient  may  feel  perfectly  well  except 
slight  weakness,  headache  or  vertigo.  He  is  usually  able  to 
attend  to  his  duties.  The  tendency  to  spontaneous  cure  is 
greater  than  in  either  of  the  other  forms  of  malaria,  the  attack 
not  infrequently  subsiding  after  a  number  of  paroxysms,  without 
any  medication  or  with  only  a  purgative. 


Oi 

\ 

U 
Q. 

s 

300 
290 
280 
270 
260 
250 
240 
230 
220 
210 
200 
190 
ISO 
170 
160 

DAY  OF 
DISEASE 

D*v  OP 

HOUR. 

: 

41°— 
40»— 
39°- 
38»- 
37°— 
36»- 

106° 
105° 
104° 
103° 
102° 
101° 
100° 
990 
98° 
970 
%° 

■■I 

\ 

:l 

1 

: 

P' 

^ 

i 

-/ 

\^ 

\- 

F 

i^ 

li- 

■*• 

Fig.   27. — Single  quartan  infection. 

Quartan  Infection. — The  quartan  parasite  accomplishes  its 
endogenous  cycle  in  seventy-two  hours.  Hence  infection  with 
a  single  generation  of  quartan  parasites  produces  a  paroxysm 
followed  by  two  days  of  apyrexia  and  a  second  paroxysm  on  the 
fourth  day.  Such  attacks  are  popularly  known  in  the  South 
as  "third-day  chills."  A  double  quartan  infection  reverses 
the  course,  causing  two  paroxysms  on  successive  days,  followed 
by  a  day  of  apyrexia.  Triple  quartan  infections,  the  parasites 
maturing  on  successive  days,  give  rise  to  quotidian  fever. 
As  in  simple  tertian  intermittents,  quartan  accesses  sometimes 
anticipate  or  retard.     Subintrance  in  triple  infections  is  rarely 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


seen,  due  probably  to  the  shorter  duration  of  the  paroxysms. 
Changes  of  type  between  single,  double,  and  triple  quartan  are 
sometimes  observed. 

The  onset,  especially  in  single  infections,  occurs  probably 
more  often  during  the  afternoon  hours.  The  symptoms  are 
those  of  the  typic  paroxysm  and  are  well  marked.  The  cold 
stage  is  not  only  more  constant  than  in  the  other  forms,  but  is 
more  intense  and  usually  of  longer  duration.  The  three  stages 
are  sharply  contrasted.     Pernicious  symptoms  are  very  rarely 


m 

D 

a. 

H 

300 
290 
280 
270 
260 
2S0 
240 
230 
220 
210 
200 
190 
180 
170 
160 

OAY  OF 
DISEASE 

Mol^T'if 

HOUR. 

410_ 
40"— 
39"— 
33»- 
37»- 
36»- 
35»- 

106° 
10S» 
104» 
103" 
102" 
101» 
100» 
990 
98° 
97° 
96° 

i 

i 

■\ 

' 

\ 

' 

\h 

V 

i: 

1- 

I* 

J; 

^: 

V 

: 

• 

Fig.   28. — Double  quartan  infection. 

observed  in  connection  with  quartan  infections.  This  maybe 
accounted  for  by  the  more  equal  distribution  through  the  cir- 
culation of  the  parasites  which  show  no  tendency  to  congregate, 
and  by  the  longer  apyrexial  periods  between  the  paroxysms. 
The  average  duration  of  the  paroxysm  is  eight  or  ten  hours. 

Estivo-autumnal  Infection.^ — The  chief  feature  of  infection 
with  estivo-autumnal  parasites  is  the  irregularity  of  the  course 
as  contrasted  with  that  of  tertian  and  quartan  infections.  A 
classification  is  difficult  and,  while  that  into  estivo-autumnal 
or  malignant  tertian  and  quotidian  is  perhaps  best,  these  may 
be  clinically  indistinguishable. 


MALARIA  103 

Malignant  Tertian. — This  form  of  infection  is  due  to  parasites 
which  tend  to  mature  in  forty-eight  hours.     It  is  characterized 


a 

f- 
< 

LU 

a 

u 

H 

300 
290 
280 
270 
260 
250 
240 
230 
220 
210 
200 
190 
180 
170 
160 

DAY  OF 
DISEASE 

^ 

"" 

■■■" 

■~ 

MONTH 

HOUR. 

41»— 
40"— 
39«- 
38»- 
37»— 
36»- 

106» 
105» 
104» 
103» 
102" 
101" 
100» 
99» 
98» 
970 
96» 

il 

'\ 

:1 

\ 

\ 

t 

\ 

'■; 

\ 

.        \ 

:l 

\ 

\ 

i       ( 

\ 

\ 

\ 

■ 

1 

\ 

\ 

'■ 

1; 

]P 

v^ 

35 

Fig.  29. — Triple  quartan  infection. 


Of 

i 

u 
a 
S 

H 

300 
290 
280 
270 
260 
250' 
240 
230 
220 
210 
200 
190 
180 
170 
160 

DAY  OF 
DISEASE 

- 

" 

■" 

S,*o1!|t1!' 

HOUR. 

410- 
40«— 
39»- 
38»- 
37»- 
36»- 
35°- 

106» 
10S» 
1040 
103» 
102" 
101» 
100" 
99° 
98° 
970 
96» 

A 

: 

J 

\\ 

\ 

, 

\ 

\ 

'■■ 

\l 

\ 

» 

f 

/' 

Vr 

■?"" 

Fig.  30. — Tertian  estivo-autumnal  malaria. 
by  a  long  paroxysm  and  a  short  apyrexia.     The  duration  of 


I04 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


the  access  is  from  twenty-four  to  forty-eight  hours  or  more. 
Anticipation  and  subintrance  are  oftener  observed  here  than 
in  any  other  form  of  malaria. 

Prodromal  symptoms  are  usually  pronounced.  The  cold 
stage  is  often  not  manifest;  the  sweating  stage  is  less  commonly 
missing.  The  typic  temperature  is  characteristic.  It  rises 
abruptly,  often  as  high  as  io4°F.  On  reaching  its  height  it 
remits  with  sUght  oscillations  for  a  few  hours.  It  then  makes  a 
marked  remission  and  again  rises  suddenly,  usually  higher  than 


Of 

s 

300 
290 
280 
270 
260 
250 
240 
230 
220 
210 
200 
190 
180 
170 
160 

DAY  OF 
DISEASE 

— 1 

MONTH 

HOUR. 

ckNI. 
41»- 

40°— 

39«- 

38»- 

370- 

36«- 

3S»- 

FAH. 

106» 
I05» 
1040 
103» 
1021" 
101» 
lOO* 
99» 
98» 
970 
96" 

: 

:] 

\ 

: 

\ 

: 

\ 

; 

■\ 

1 

■ 

- 

-V 

f 

A 

■;A 

/ 

I; 

I 

i 

f 

1^ 

Fig.  31. — Quotidian  estivo-autumnal  malaria. 

before.  The  final  fall  is  by  crisis.  It  is  customary,  following 
Marchiafava  and  Bignami,  to  divide  this  course  into  five  stages: 
(i)  the  rise  of  invasion;  (2)  the  fastigium;  (3)  the  pseudocrisis; 
(4)  the  precritical  rise;  (5)  the  crisis.  This  curve  is  simulated 
only  by  simple  tertian  fever  with  subintrant  attacks,  which  is 
uncommon.  Unfortunately  this  typic  sequence  is  far  from 
constant;  the  modifications  are  very  numerous  and  are  too  ir- 
regular to  analyze. 

The  symptoms  of  the  hot  stage  are  more  pronounced  than  in 
the  infections  previously  described.  The  headache  and  back- 
ache are  worse,  the  general  depression  is  more  profound,  stupor 


MALARIA  105 

and  delirium  may  appear  and  pernicious  symptoms  may  arise. 
During  the  short  interval  the  patient  does  not  regain  his  ease  as 
in  the  simple  intermittent  fevers,  but  the  aching  and  prostra- 
tion continue,  and  he  may  be  unaware  that  the  fever  has  left. 

Quotidian. — The  quotidian  estivo-autumnal  fever  is  more 
regular  in  its  course  than  the  tertian,  especially  at  first,  though 
there  is  nothing  characteristic  in  the  temperature  curve,  which 
may  closely  resemble  a  double  tertian  or  a  triple  quartan.  Later 
it  is  apt  to  lose  some  of  its  regularity  by  anticipation  or  by 
lengthening  of  the  paroxysms,  whose  average  duration  is  from 
six  to  ten  hours.  The  chill  is  rather  more  constant  than  in 
the  tertian;  otherwise  the  symptoms  are  identical,  the  patient 
not  regaining  strength  from  one  paroxysm  to  another.  In 
the  interval  the  temperature  is  prone  to  sink,  even  as  low  as 
to  95°F. 

Mixed  Infections. — Infections  with  two  or  more  species  of 
the  malaria  parasite  are  known  as  mixed  or  combined  infections. 
The  most  frequent  combination  is  of  simple  tertian  and  estivo- 
autumnal.  As  a  rule,  one  parasitic  form  predominates  and 
produces  its  usual  picture;  this  may,  however,  be  considerably 
modified  by  the  other  group  of  parasites.  The  most  frequent 
modification  in  the  temperature  chart  is  a  tendency  to  con- 
tinuity. The  paroxysms  are  not  usually  as  typic  as  in  simple 
infections  and  are  not  so  regular  in  their  occurrence. 

Analysis  of  Symptoms. — Temperature. — The  main  charac- 
teristics of  malarial  temperature  have  been  given  when  treating 
of  the  several  forms.  It  remains  only  to  consider  a  few  general 
traits. 

The  feature  of  the  temperature  in  uncomplicated  and  un- 
treated malaria  is  periodicity.  The  temperature  is,  in  a  great 
majority  of  instances,  intermittent. 

In  tertian  and  quartan  infections  the  temperature  usually 
rises  rapidly  after  the  onset,  reaching  the  acme  during  the 
second  stage  of  the  paroxysm  and  declining  during  the  third 
to  normal  or  a  little  below  normal.  This  is  also  the  usual  course 
in  quotidian  estivo-autumnal,  the  temperature  chart  showing 
symmetric  ascent  and  descent,  producing  an  arrow-head  ap- 
pearance.    In  this  infection  the  temperature  descends  rather 


Io6  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

lower  during  the  fever-free  interval  than  in  the  others.  The 
typic  run  of  tertian  estivo-autumnal  has  been  given  as  follows : 
(i)  the  stage  of  initial  ascent;  (2)  the  fastigium,  during  which 
the  temperature  may  show  fluctuations  of  a  half  degree  to  a 
degree;  (3)  the  pseudocrisis;  (4)  the  precritical  or  final  ascent; 
and  (5)  the  crisis. 

Continued  temperature  in  malaria  is  not  as  common  as  usually 
regarded;  remittent  fever  was  formally  thought  to  be  the  rule 
in  the  summer-autumn  malarial  fevers.  The  causes  of  this 
error  are  three:  first,  in  tertian  estivo-autumnal  infections  the 
apyretic  interval  is  short;  second,  this  interval  often  occurs 
during  the  night  or  early  morning  hours;  thirdly,  the  patient, 
guided  by  the  discomfort  which  continues  during  the  interval, 
usually  denies  that  he  has  been  free  from  fever.  Nevertheless, 
a  continued  temperature  is  occasionally  noted  in  malaria,  espe- 
cially in  tertian  estivo-autumnal  infections. 

The  duration  of  untreated  acute  malaria  is  too  indefinite  to 
permit  of  exact  statements.  While  simple  tertian  may  ter- 
minate after  a  few  paroxysms,  an  estivo-autumnal  fever  may 
continue  three  or  four  weeks  if  it  does  not  in  the  meantime 
become  pernicious. 

A  post-malarial  secondary  fever,  or  spodogenous  fever,  is 
occasionally  observed  after  the  infection,  particularly  estivo- 
autumnal,  has  lasted  for  some  time.  It  persists  for  days  or 
weeks  uninfluenced  by  quinine.  The  blood  examination  is 
negative  for  parasites. 

Circulatory  System. — The  Blood. — The  volume  of  the  blood 
as  a  whole  is  somewhat  diminished.  The  specific  gravity  is 
only  slightly  lowered,  and  usually  only  nearly  compensated  by 
the  excretion  of  fluids.  The  density,  at  first  lowered,  approaches 
normal  as  the  infection  persists.  The  experiments  that  have 
been  performed  with  reference  to  the  tonicity  of  the  blood  in 
malaria  have  uniformly  shown  that  this  is  increased. 

The  tertian  parasite,  more  abundant  in  the  deep  circulation, 
may  be  observed  in  the  peripheral  circulation  throughout  the 
course  of  the  asexual  cycle,  excepting  the  sporulating  forms, 
which  are  only  exceptionally  seen.  The  gametes  are  not  in- 
frequently detected. 


MALARIA  107 

The  quartan  parasite  is  most  evenly  distributed,  being  about 
equally  common  in  the  visceral  and  superficial  blood.  Further- 
more, all  stages  of  the  asexual  development,  including  the 
sporulating  forms,  may  be  followed  in  blood  obtained  from  the 
peripheral  circulation.     Quartan  gametes  are  rarely  seen. 

The  estivo-autumnal  parasites  are  seen  only  in  the  earliest 
phases.  In  some  localities  the  gametes  are  very  commonly 
observed  after  the  infection  has  persisted  a  week  or  more; 
in  others,  even  where  severe  infections  of  long  standing  are 
encountered,  they  are  more  rarely  noted. 

Pigment  is  most  frequently  contained  within  the  large  mono- 
nuclear, less  often  the  polymorphonuclear,  leucocytes,  but  may 
exist  free  in  the  blood  current.  It  is  of  a  dark  reddish-brown 
or  black  color,  and  occurs  as  granules,  rodlets,  or  irregular 
clumps. 

One  of  the  best-known  facts  in  the  study  of  malaria  is  the 
rapid  and  widespread  destruction  of  the  red  blood-cells.  A 
certain  number  of  erythrocytes  perish  with  each  parasitic 
sporulation  like  soldiers  after  a  volley  from  the  enemy.  It  is 
not  uncommon  for  a  fourth  to  a  half  million  red  cells  per  cubic 
millimeter  to  be  destroyed  during  each  of  the  first  two  or  three 
paroxysms,  and  this  may  progress  until  the  count  is  con- 
siderably less  than  one  million  per  cubic  millimeter.  The 
anemia  is  commonly  in  proportion  to  the  severity  and  duration 
of  the  attack.  Restitution  of  the  red  cells  is  more  rapid  and 
certain  with  tertian  and  quartan  than  with  estivo-autumnal 
infections.  Race,  age,  and  constitution  are  also  factors  in 
the  rapidity  of  reconstruction. 

The  cells  containing  the  simple  tertian  parasites  are  swollen 
and  somewhat  decolorized.  Those  containing  the  quartan 
parasites  are  shrunken  and  somewhat  darker  in  color.  The 
cells  harboring  estivo-autumnal  organisms  have  the  appear- 
ance of  old  gold  or  of  brass,  and  become  somewhat  smaller. 
A  curious  appearance  of  some  infected  cells  is  what  has  been 
termed  stippling.  This  may  be  seen  in  both  simple  tertian  and 
estivo-autumnal  infections,  but  presents  features  more  or  less 
characteristic  in  each.  In  simple  tertian  the  dots  are  fine  and 
abundant.     In    estivo-autumnal    they    are    coarse,    irregular, 


Io8  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

may  be  cleft-like,  and  few  in  number — from  two  to  six.  The 
fine  stippling  of  tertian  infection  is  also  known  as  "Schiiffner's 
dots."     Stippling  is  brought  out  by  staining. 

Changes  occur  also  in  non-infected  cells.  The  commonest 
of  these  are,  in  my  experience,  in  the  order  named:  the  occur- 
rence of  macrocytes  and  microcytes,  polychromatophiles,  and 
poikilocytes.  Nucleated  reds  are  occasionally  observed.  Baso- 
phile  granulation  is  sometimes  noted. 

Retraction  of  hemoglobin  and  vacuolization  are  common 
findings  in  malarial  blood. 

The  hemoglobin  generally  falls  decidedly.  Its  curve  is  apt 
to  run  parallel  with  and  a  little  below  that  of  the  red  cells, 
and  is  slower  in  returning  to  normal.  The  hemoglobin  content 
is  no  guide  as  to  the  severity  of  the  disease. 

The  leucocytes  are,  in  benign  malaria,  usually  slightly  di- 
minished. A  leucocytosis  is  found  only  in  pernicious  malaria 
or  in  association  with  complications.  The  differential  formula 
is  the  most  noteworthy  feature.  Its  peculiarity  is  the  large 
mononuclear  increase.  Eosinophilia  in  my  experience  denotes 
complications,  ordinarily  intestinal  helminthiasis. 

The  leucocytes  occasionally  undergo  degenerative  changes, 
among  which  are  fatty  degeneration  and  vacuolization  of 
the  protoplasm  and  fragmentation  and  chromatolysis  of  the 
nucleus. 

The  blood  platelets  are  somewhat  increased  in  malaria,  es- 
pecially during  the  interval  following  a  severe  attack. 

The  Wassermann  reaction  is  occasionally  positive  in  malaria. 
Of  1,957  cases  of  diseases  other  than  syphilis  examined  by  Craig 
and  Nichols, ''°-  four  of  the  positive  cases  were  in  patients  with 
malaria.  In  forty-six  cases  of  malaria,  Boehm^"^  found  the 
Wassermann  positive  in  sixteen  cases  or  34.8  per  cent. 

Sutherland  and  Mitra'*'^  examined  the  blood  of  fifty  patients 
in  whom  parasites  were  present  and  nine  gave  positive  Wasser- 
manns;  at  least  three  were  probably  syphilitic. 

At  the  height  of  the  fever  the  pulse  may  reach  130  or  more. 
During  the  interval  it  usually  becomes  almost  quite  normal  in 
tertian  and  quartan  infections.  In  estivo-autumnal  fever  it 
depends  upon  the  severity  of  the  attack  and  the  resistance  of 


MALARIA  109 

the  patient.  An  anemic  murmur  may  be  heard  ove-r  the  heart. 
A  sense  of  precordial  oppression  or  acute  pain  are  common 
complaints. 

Respiratory  Organs. — Respiration  is  usually  accelerated  in 
proportion  to  the  temperature.  Cough  is  a  frequent  symptom. 
In  children  a  frequently  repeated  superficial  hacking  cough  is 
often  an  indication  of  nausea.  Bronchial  catarrh  is  not  in- 
frequently observed,  accompanied  by  sibilant  rales  on  auscul- 
tation. Epistaxis  may  occur  and  is  occasionally  alarmingly 
profuse. 

Gastro-intestinal  Organs. — While  the  paroxysm  is  on,  the  ap- 
petite is  usually  completely  lost.  In  tertian  and  quartan 
malaria  this  may  be  regained  during  the  interval,  but  in  estivo- 
autumnal  anorexia  generally  persists  throughout  apyrexia. 
The  patient  ordinarily  complains  of  a  bitter  taste  in  the  mouth 
and  fulness,  discomfort  or  pain  in  the  epigastric  region.  The 
tongue  is  large,  flabby,  thickly  coated,  usually  anemic,  and 
showing  the  prints  of  the  teeth  along  the  edges.  Nausea  is 
nearly  a  constant  symptom,  and  retching  and  vomiting  are 
distressing.  The  vomitus  consists  of  matters  ingested,  bile 
or  slimy  mucus.  The  bowels  are  constipated,  regular,  or  loose, 
in  the  order  of  frequency  named;  choleraic  or  dysenteric 
discharges  occasionally  appear.  More  or  less  enlargement  of 
the  spleen  is  a  usual  occurrence,  together  with  pain  and  tender- 
ness in  the  left  hypochondrium.  In  primary  acute  infections 
the  enlargement  may  not  be  prominent;  in  later  infections  the 
spleen  is  often  palpable  beyond  the  costal  margin.  The  spleen 
is  rarely  much  enlarged  in  the  negro.  Enlargement  of  the  liver 
is  much  less  contant  and  less  marked  than  splenic  hj^ertrophy. 
There  usually  exists  tenderness  in  the  epigastric  and  right  hy- 
pochondriac regions. 

Genito-urinary  Organs. — Urine. — As  a  general  rule,  the  urine 
emitted  during  a  cold  stage  is  pale  in  color  and  that  of  the 
stage  of  fever  highly  colored,  but  individual  circumstances  may 
produce  numerous  exceptions  to  this  rule.  In  certain  cases  of 
estivo-autumnal  fever  the  urine  may  be  very  highly  colored 
and  contain  a  heavy  deposit.  In  these  cases  the  urine  contains 
biliary  coloring  matters  and  an  excess  of  urobilin.     The  diazo 


no  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

reaction  sometimes  obtains.  The  indican  is  frequently  in- 
creased. In  tertian  and  quartan  cases  the  quantity  of  the  urine 
is  somewhat  augmented,  in  estivo-autumnal  diminished.  The 
reaction  is  acid,  varying  directly  with  the  concentration  of 
the  urine.  The  specific  gravity  does  not  always  bear  a  definite 
relation  to  the  amount  of  the  urine,  as  might  be  inferred,  but 
may  be  relatively  high  when  the  urine  is  abundant,  or  low  with 
scanty  urine. 

The  output  of  urea  is  increased.  The  increase  begins  several 
hours  before  the  attack,  attains  its  maximum  toward  the  end 
of  the  cold  stage,  declining  to  or  below  normal  at  the  end  of  the 
paroxysm. 

The  uric  acid  content  of  the  urine  is  only  shghtly,  if  at  all, 
modified.  The  amount  of  chlorides  runs  parallel  with  the' 
quantity  of  urine.  The  phosphates  are  eliminated  in  quantities 
less  than  normal  during  the  fever,  and  in  greater  quantities 
during  apyrexia.  The  entire  twenty-four-hour  urine  com- 
monly shows  an  increase.  The  variations  in  the  excretion  of 
the  sulphates  are  similar  to  those  in  regard  to  urea. 

The  ehmination  of  the  sodium  and  potassium  bases  is  very 
inconstant,  both  as  to  quantity  and  as  to  the  stage  of  the 
disease  during  which  elimination  takes  place.  Malarial  urine 
contains  an  excess  of  iron,  especially  after  the  paroxysm.  It 
is  dependent  upon  and  proportionate  to  the  destruction  of 
erythrocytes. 

The  occurrence  of  albumin  in  the  urine  is  relatively  infrequent 
in  the  mild  attacks  of  simple  intermittent  which  terminates 
after  one  or  two  paroxysms.  In  severe  estivo-autumnal  in- 
fections, however,  it  is  exceedingly  frequent.  Its  frequency 
varies  not  only  with  the  type  and  severity  of  the  attack,  but 
also  with  locality  and  other  circumstances.  The  following 
reports  are  tabulated  to  show  the  extent  of  these  differences, 
the  denominator  indicating  the  number  of  cases  of  malaria, 
the  numerator  the  number  in  which  albumin  was  found: 


Costa^s ^2— 

103 

F.  Plehn2 -^ 


MALARIA  III 


39 


Marchoux'- 

40 

Borne,""  per  cent 3 .8 

133 

Thaver  and  Heweston'"' ' — - 

335 

Solon, ^'  per  cent 25 

Schoo,"  per  cent 2 

321 

7S8 

14 
1780 


Thayer'"*. 
Anders*  "=. 
Atkinson*' 


121 

o 
Chamberlain*'" 

120 

20 

Frericks'" — 

SI 

Cook*"'' .■ -^ 

100 

An  increased  toxicity  of  the  urine  has  been  found  in  a  large 
per  cent,  of  cases  of  malaria,  greatest  during  apyrexia  and 
usually  intensifying  with  each  successive  paroxysm. 

Nervous  System. — Headache  is  one  of  the  most  invariable 
symptoms  of  malaria.  Backache  and  somatic  soreness  are 
severe.  Sometimes  hyperesthesia  is  seen.  Vertigo  is  the  rule, 
especially  when  the  patient  is  upright.  Neuralgia,  facial  or 
intercostal,  is  a  not  infrequent  symptom.  Stupor  and  delirium 
are  present  in  grave  cases,  particularly  in  children. 

Skin. — During  the  first  stage  of  the  paroxysm  the  skin  is 
blanched  and  cold;  during  the  second  stage  hot,  dry,  and  per- 
haps turgid;  during  the  third  bathed  with  sweat,  becoming 
natural  toward  apyrexia.  Icterus  is  not  a  pronounced  symptom 
in  acute  cases  except  in  certain  pernicious  forms.  With  the 
possible  exception  of  pneumonia,  herpes  is  seen  more  frequently 
in  malaria  than  in  any  other  disease.  Its  commonest  sites  are 
the  lips  and  nose,  but  it  may  appear  elsewhere.  It  is  not  nearly 
so  common  in  the  negro  as  in  the  white.  Urticaria  and  erythema 
are  sometimes  observed. 

PERNICIOUS  MALARIA 

Pernicious  malaria  is  that  form  of  malaria,  extremely  acute, 
which,  independently  of  complications,  endangers  life  in  a  few 


112  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

hours  or  a  few  days.  This  gravity  may  be  due  to  the  intensifi- 
cation of  ordinary  malarial  symptoms  or  to  the  advent  of 
unusual  ones.  It  should  be  clearly  understood  that  pernicious 
fever  is  not  a  pathologic  entity,  but  is  a  form  of  malaria  from 
the  simple  modes  of  which  it  sometimes  differs  only  in  degree. 
Its  pathogenesis  is  intimately  associated  with  the  life  history 
of  the  malaria  parasite,  much  more  so  than  is  hemoglobinuric 
fever.  Intermediate  forms  may  be  encountered  which  may  be 
difficult  to  place,  as  cases  with  slight  somnolence,  abundant 
sweats,  or  cold  surface. 

More  than  thirty  so-called  varieties  of  pernicious  malaria 
have  been  described.  A  partial  list  of  these  includes  the  apo- 
plectic, ataxic,  comatose,  sudoral  or  diaphoretic,  delirious, 
eclamptic  or  convulsive,  tetanic,  typhoid,  amaurotic,  aphasic, 
ardent,  exanthematous,  hemiplegic,  hydrophobic,  neuralgic, 
cerebromeningeal,  cardialgic,  dyspneic  or  asthmatic,  pneu- 
monic, pleuritic,  syncopal,  hemoptoic,  algid,  choleraic,  dysen- 
teric, gastric  or  gastralgic,  hemorrhagic,  bilious  or  hepatic, 
lymphatic,  rheumatic  and  nephritic  forms. 

Any  classification  is  not  absolutely  essential,  and  all  are  more 
or  less  arbitrary.  Nevertheless,  for  convenience,  all  forms  of 
true  pernicious  malaria  may  be  easily  and  logically  arranged  into 
(i)  cerebrospinal,  (2)  thoracic,  and  (3)  abdominal  forms. 

Cerebrospinal  Forms. — The  representative  type  of  cere- 
brospinal pernicious  malaria  is  the  comatose  variety,  which  is, 
as  well,  the  most  frequent  of  all  varieties. 

Comatose  malaria  may  make  its  appearance  as  the  first 
manifestation  of  malaria  or,  more  commonly,  after  the  lapse 
of  one  or  more  paroxysms,  typic  or  irregular.  Violent  headache, 
stupid  countenance,  and  somnolence  interrupted  by  frequent 
sighing,  with  a  mild  grade  of  mental  aberration  and  defective 
articulation  and  vision,  are  not  uncommon  prodromata.  These 
may,  however,  be  so  sHght  as  to  escape  notice.  The  onset  of 
cerebral  symptoms  may  be  with  violent  abruptness  (the  apo- 
plectic form  of  some  writers)  or,  as  is  most  common,  begin 
within  a  few  hours  after  the  commencement  of  the  paroxysm 
with  somnolence,  which  gradually  deepens  into  stupor  and 
coma.     It  has  occasionally  happened  that  malarial  coma  has 


MALARIA  113 

come  on  during  natural  sleep,  the  condition  of  the  patient  being 
discovered  by  accident.  Convulsions  may  precede  the  coma, 
especially  in  children,  or  there  may  be  extreme  restlessness, 
gritting  the  teeth,  and  jactitation.  The  cerebral  symptoms  may 
vary  from  the  marked  drowsiness  to  profoundest  coma.  The 
eyes  may  be  closed  or  open  (coma- vigil) .  The  pupils  are  usually 
equal  and  dilated  or  contracted,  but  may  be  unequal  and  may 
or  may  not  react  to  light.  Strabismus  is  an  occasional  symp- 
tom. The  face  is  congested  in  individuals  recently  attacked 
or  pallid  in  older  sufferers.  The  skin  is  at  first  hot  and  dry, 
perhaps  slightly  jaundiced;  later  it  may  be  bathed  with  sweat. 
Petechias  are  occasionally  seen.  Trismus  may  be  present,  but 
the  extremities  are  usually  completely  relaxed,  though  sensation 
and  motion  are  often  not  entirely  abolished,  as  sometimes 
evidenced  by  resistance  to  hypodermic  medication.  Cases 
manifesting  muscular  rigidity  and  tonic  contractures  have 
been  reported.  Hyperesthesia  and  muscular  tremors  are  not 
infrequently  present.  The  reflexes  may  be  increased  or 
diminished. 

There  may  be  twitching  of  the  muscles  of  the  face,  usually 
confined  to  one  side.  Loud  calls  may  not  elicit  response,  and 
shaking  only  groans  and  unintelligible  utterances.  The  coma 
may  be  intermittent,  running  parallel  with  the  temperature. 
The  fever  in  most  cases  varies  from  101°  to  io3°F.,  but  may  be 
subnormal  or  hyperpyrexia!.  The  pulse  is  at  first  full  and 
bounding,  later  small,  rapid,  and  feeble.  Dilatation  of  the  right 
side  of  the  heart  may  exist  and  an  anemic  murmur  may  some- 
times be  heard.  The  respiration  may  be  quiet,  slow  or  rapid, 
or  blowing  and  stertorous,  with  Cheyne-Stokes  characteristics 
late  in  the  course.  Edema  of  the  lungs  is  an  occasional  late 
occurrence.  Nausea  and  vomiting  are  seen  early  in  the  attack, 
if  they  are  present  at  all.  The  mouth  and  tongue  are  dry, 
the  latter  deeply  coated.  Herpes  and  sordes  ate  sometimes 
noted.  Hiccough  is  an  occasional  symptom.  The  tongue  when 
protruded  may  be  drawn  to  one  side.  In  cases  of  recent 
infection  the  spleen  may  be  only  slightly  or  not  at  all  enlarged; 
in  other  cases  it  may  be  greatly  enlarged,  constituting  a  valuable 
diagnostic  sign. 


114  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

The  liver  may  be  tender,  but  is  usually  not  much  enlarged. 
The  evacuations  of  bowels  and  bladder  may  be  involuntary 
or  there  may  be  retention  of  urine.  The  bowels  are  often 
constipated. 

In  favorable  cases  the  coma  gradually  fades,  consciousness 
slowly  dawns,  the  temperature  drops  to  or  below  normal,  the 
pulse  regains  its  normal  characteristics,  and,  save  the  physical 
weakness  and  a  degree  of  mental  hebetude,  all  is  well  with  the 
patient. 

In  unfavorable  cases  the  coma  becomes  absolute,  the  pulse 
becomes  rapid,  thready,  and  irregular,  the  breathing  is  stertor- 
ous and  of  Cheyne-Stokes  type,  tracheal  rattling  appears,  the 
face  becomes  cyanotic,  and  death  ensues  from  convulsions  or 
from  collapse. 

The  duration  of  an  attack  is  from  a  few  hours  to  a  few  days. 

It  usually  holds  true  that  the  successive  paroxysms  increase 
in  severity  and  danger  to  the  patient.  In  the  interval  the 
patient  may  be  apathetic  or  may  complain  of  headache.  The 
relapse  may  appear  in  the  form  of  a  different  type  of  pernicious 
paroxysm,  as  algid  or  choleraic,  but  such  cases  are  very  rare. 

As  intimated,  the  apoplectic  form  of  pernicious  malaria  is 
merely  a  fulminant  variety  of  comatose  malaria.  In  these  rare 
cases  the  onset  is  equally  as  sudden  as  in  cerebral  hemorrhage, 
whence  the  name. 

Symptoms  originating  from  the  cerebellum  are  present  in 
rare  instances.  Such  are  slow,  monotonous  speech,  drowsiness, 
severe  depression  and  incoordination  of  voluntary  movements. 

Cases  in  which  hemiplegia  occurs  have  sometimes  been 
described  as  the  hemiplegic  form  of  pernicious  malaria;  cases 
with  aphasia,  as  the  aphasic  form.  These  two  are  not  infre- 
quently associated.  Paraplegia  is  a  very  rare  development 
in  pernicious  malaria. 

A  mild  delirium  is  frequently  present  in  the  cerebrospinal 
forms  of  pernicious  malaria.  When  it  is  conspicuous  it  forms 
the  so-called  delirious  type.  In  this  probably  more  than  in 
any  other  form  do  predispositions  have  a  causal  part,  especially 
alcoholism,  nervous  predisposition,  mental  fatigue,  and  ex- 
posure to  solar  heat.     Delirium  in  this  condition  may  vary 


MALARIA  IIS 

from  quiet  to  maniacal.  Cases  resembling  rabies  have  been 
designated  intermittens  hydro phohica. 

Convulsive  or  eclamptic  pernicious  malaria  is  a  variety  of 
the  comatose  type  in  which  convulsions  are  a  prominent  fea- 
ture. It  is  especially  common  in  children.  The  convulsions 
may  be  confined  to  certain  muscle  groups  or  may  be  general. 
In  one  of  my  cases  the  little  patient  had  twelve  convulsions  in 
an  hour.  Epileptiform  convulsions  have  been  described,  but 
it  is  probable  that  most  of  these  cases  are  complicated  with 
true  epilepsy. 

The  most  prominent  symptoms  are  usually  trismus  and  opis- 
thotonos; emprosthotonos  and  pleurosthotonos  are  but  rarely 
observed. 

Occasionally  amaurosis  arises  in  the  course  of  a  comatose 
attack.  It  may  be  transient  or,  in  rare  instances,  permanent. 
In  the  only  case  occurring  under  my  observation  vision  began 
to  improve  at  the  end  of  the  attack,  but  was  not  fully  restored 
until  after  several  weeks. 

A  rare  form  of  pernicious  malaria,  the  ataxic,  has  been 
described.  The  principal  symptoms  are  scanning  speech, 
dysarthria,  weakness  of  lower  limbs,  vertigo,  unsteady  gait  with 
a  disposition  to  fall  forward,  muscular  tremors,  and  exag- 
gerated reflexes. 

Manson^^  thus  describes  the  so-called  ardent  fever:  "In 
the  course  of  what  seems  to  be  an  ordinary  malarial  attack 
the  body  temperature,  instead  of  stopping  at  104°  or  io5°F., 
may  continue  to  rise  and,  passing  io7°F.,  rapidly  mount  to 
110°  or  even  to  ii2°F.  The  patient,  after  a  brief  stage  of  wild, 
maniacal,  or  perhaps  muttering  delirium,  becomes  rapidly 
unconscious,  then  comatose,  and  dies  within  a  few  hours  or 
perhaps  within  an  hour  after  the  onset  of  the  pernicious 
symptoms." 

In  typhoid  pernicious  the  clinic  picture  is  almost  identical 
with  that  presented  in  typhoid  fever.  The  temperature  is 
periodically  intermittent  or,  as  is  more  common,  remittent,  and 
usually  ranges  from  101°  to  i03°F.,  but  may  reach  io6°F. 
There  are  headache,  backache,  rapid  pulse,  torpid  digestive 
tract,  sordes,  splenomegaly,  apathy,  and  stupor.     There  may 


Il6  ENDEMIC    DISEASES    OE    THE    SOUTHERN    STATES 

be  diarrhea  or  constipation,  and  bilious  vomiting  occurs  in 
some  cases.  The  abdomen  is  usually  tympanitic  and  there  may 
exist  tenderness  and  gurgling  in  the  right  ihac  fossa.  Epistaxis 
is  frequent.  Incoherent  speech,  delirium,  and  incontinence 
of  urine  and  feces  are  symptoms  of  severe  cases. 

Thoracic  Forms. — The  immunity  of  the  organs  of  the  chest 
to  locahzations  of  the  malarial  parasites  and  to  the  effects  of 
their  toxins  is  remarkable.  Indeed,  the  thoracic  forms  are 
much  rarer  than  the  records  would  import,  for  the  older  writers 
especially  were  prone  to  attribute  any  complication  that  might 
present  itself  to  the  effect  of  the  mysterious  malarial  poison. 

Formerly  cases  of  pneumonic  pernicious  malaria  were  more 
frequently  reported  than  at  present.  Since  more  exact  methods 
of  observation  have  come  into  use  it  is  certain  that  many  of 
these  cases  were  complicating  lobar  pneumonias.  That  the 
malarial  parasite  is  unable  to  cause  true  inflammation  of  lung 
tissue  is  now  widely  recognized.  Nevertheless  grave  symptoms 
referable  to  the  lung,  and  more  or  less  resembling  pneumonia, 
may  arise  in  malarial  infections.  Cases  presenting  profuse  hem- 
orrhages from  the  lungs  and  nose  have  been  recorded  but  rarely. 

Abdominal  Forms. — The  type  of  abdominal  pernicious 
malaria  is  the  algid.  The  picture  presented  is  that  of  abdom- 
inal shock;  it  is  peritonism  minus  the  peritonitis. 

The  algid  symptoms  may  appear  insidiously,  but  much  more 
frequently  supervene  after  the  course  of  one  or  more  simple 
paroxysms.  Usually  the  first  symptoms  that  attract  the  atten- 
tion to  the  condition  of  the  patient  are  the  bad  pulse  and  cold 
surface.  Soon  the  Hippocratic  facies  is  assumed.  The  eyes 
are  deeply  sunken  and  surrounded  by  dark  circles,  the  nose 
appears  sharp,  the  alae  nasi  dilate  with  respiration,  the  tip  of 
the  nose  and  the  ears  are  icy  cold.  The  temples  and  cheeks  are 
hollowed,  the  cheek  bones  project,  the  pupils  are  dilated,  the 
conjunctivae  are  bluish  white,  the  eyes  have  a  peculiar  anxious 
expression,  and  the  breath  is  cool.  The  skin  is  pale,  having  the 
appearance  of  absolute  bloodlessness  rather  than  that  of  cy- 
anosis. The  surface  of  the  body  is  bathed  with  a  clammy  sweat, 
is  cold,  and  gives  the  sensation  to  the  hand  of  handling  a 
catfish.     The  fingers  and  toes  often  have  the  shrunken  appear- 


MALARIA  117 

ance  of  the  washerwoman's  hand.  The  prostration  is  extreme 
and  the  voice  is  weak,  low,  and  cracked.  The  patient  complains 
of  burning  heat  within  and  begs  piteously  for  cold  drinks,  which 
are,  as  a  rule,  immediately  rejected  by  the  stomach.  The 
intelligence  remains  clear  and  occasionally  "the  patient,  over- 
come by  sad  apprehensions,  considers  himself  lost,  bewails 
his  situation,  but  is  not  delirious,"  though  usually  he  is  in- 
different to  his  peril.  The  temperature  may  be  subnormal  or 
slightly  elevated,  seldom  reaching  i04°F.  The  pulse  is  rapid, 
filiform,  of  low  tension,  and  often  intermittent.  Later  it 
usually  becomes  imperceptible  at  the  radial.  The  heart  sounds 
are  extremely  feeble.  The  respiration  is  very  rapid,  superficial, 
and  frequently  interrupted  with  deep  sighs.  The  tongue  is 
tremulous,  cold,  and  usually  moist  and  smooth.  Vomiting  is 
a  common  symptom.  The  bowels  are  sometimes  constipated, 
but  often  loose.  The  abdomen  may  be  slightly  tympanitic, 
or  scaphoid  and  tender,  especially  in  the  upper  half.  The 
urine  is  scanty,  highly  colored,  and  of  high  specific  gravity. 
The  duration  of  the  attack  is  short,  rarely  longer  than  twelve 
hours  after  the  onset  of  algidity.  In  fatal  cases  the  symptoms 
progress  rapidly  and  the  patient  dies  as  if  in  peaceful  sleep. 
In  favorable  cases  the  character  of  the  circulation  and  respiration 
improves,  the  body  warmth  is  gradually  restored,  the  patient 
ceases  to  complain,  and  convalescence  is  impeded  only  by  the 
extreme  weakness. 

When,  in  addition  to  the  symptoms  of  algidity  already  de- 
tailed, there  exist  symptoms  simulating  true  cholera,  there  is 
the  variety  of  algid  malaria  usually  spoken  of  as  choleraic  per- 
nicious. The  onset  is  with  profuse  diarrhea  and  vomiting. 
The  stools  are  thin  and  watery  and  often  rice-water-like.  There 
may  likewise  be  shown  the  muscular  cramps  of  the  lower 
limbs  frequent  in  cholera.  The  temperature  is  usually  elevated, 
and  pains  in  the  abdomen  and  precordia  and  singultus  may 
be  experienced.  The  urine  is  usually  scanty  and  may  become 
suppressed. 

The  condition  of  algor  with  which  drenching  diaphoresis 
occurs  constitutes  the  so-called  sudoral  or  diaphoretic  form  of 
pernicious  fever.     These  sweats,  which  are  so  profuse  that  not 


Il8  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

only  the  clothing  of  the  patient,  but  also  the  bedclothes  are 
saturated,  usually  supervene  toward  the  close  of  a  paroxysm. 
The  celebrated  Torti,  who  was  himself  the  victim  of  such  an 
attack,  says  that  he  was  just  congratulating  himself  upon 
escaping  the  fever  when  the  abundant  sweats  occurred  to  con- 
vince him  that  his  condition  was  critical. 

In  the  course  of  an  algid  access  syncope  occasionally  occurs 
when  any  exertion,  even  the  slightest,  is  attempted  or  when  the 
patient's  head  is  lifted  from  the  pillow.  This  dangerous  symp- 
tom usually  comes  quite  unexpectedly,  and  if  the  patient  sur- 
vives the  first  onset  a  subsequent  one  may  rapidly  prove  fatal. 

The  gastralgic  or  cardialgic  type  is  characterized  by  excru- 
ciating pain  in  the  abdomen,  especially  the  epigastric  region, 
or  in  the  precordia.  The  pain  is  often  so  intense  that  the  patient 
doubles  up  and  rolls  in  agony  upon  the  bed.  The  abdomen  is 
tender  and  vomiting  is  a  common  symptom.  There  may  be 
hematemesis,  sometimes  profuse.  Diarrhea  and  singultus  are 
occasionally  symptoms. 

The  frequent  occurrence  of  severe  dysenteric  symptoms, 
due  solely  to  malarial  infection,  has  been  definitely  demon- 
strated. The  attack  may  follow  other  forms  of  abdominal  per- 
nicious or  may  come  on  suddenly.  There  are  frequent  actions 
of  bloody  mucus,  violent  tenesmus,  colicky  pains  in  the  abdo- 
men, elevation  of  temperature,  and  sometimes  emaciation.  Algid 
symptoms  are  not  common.  Occasionally  abundant  hemor- 
rhages from  the  bowels  occur.  They  may  prove  rapidly  fatal, 
especially  if  the  patient  is  already  markedly  anemic. 

Icterus  and  bilious  vomiting  are  not  rare  in  malaria.  As  a 
rule,  these  are  not  grave  symptoms,  but  there  are  cases  in  which 
their  persistence  and  intensity  form  a  complex  of  symptoms 
described  as  bilious  pernicious  malaria.  The  fever  is  usually 
high,  nausea  constant,  icterus  marked,  and  vomiting  of  bile 
distressing.  Bile  is  present  in  the  urine,  often  in  quantities, 
and  sometimes  albumin.  Epistaxis  and  hematemesis  have 
been  noted.  The  epigastrium  is  often  painful  and  singultus 
may  add  to  the  discomfort  of  the  patient.  Toward  the  end 
of  the  severe  cases  there  are  apathy  and  carphology  and  the 
scene  usually  closes  with  delirium  and  coma. 


MALARIA  119 

Cases  are  not  rarely  observed  in  which  the  symptoms  closely 
simulate  peritonitis,  and  cases  have  even  been  operated  upon 
for  appendicitis. 

The  urine  is  usually  highly  colored.  The  amount  varies 
inversely  with  the  quantity  of  sweat,  bowel  movement,  and 
vomited  matter;  the  specific  gravity  varies  inversely  with  the 
amount.  Early  in  the  attack  albumin  may  be  absent,  though 
later  it  is  often  present  in  large  quantities,  together  with  numer- 
ous tube  casts. 

The  blood  in  various  forms  of  pernicious  malaria  shows, 
besides  parasitic  findings  previously  mentioned,  a  pronounced 
reduction  of  red  cells,  averaging  a  half  to  one  million  per 
paroxysm.  Polychromatophilia  of  red  cells  may  be  observed. 
Contrary  to  the  case  of  simple  malaria,  there  is  usually  a  pro- 
nounced leucocytosis.  There  may  be  as  many  as  35,000  per  cubic 
millimeter. 

CHRONIC  MALARIA 

There  is  a  great  deal  of  confusion  as  to  what  is  comprehended 
by  chronic  malaria.  Much  of  this  chaos  is  due  to  including 
the  manifestations  of  malarial  cachexia  with  those  of  chronic 
malaria,  between  which,  however,  there  are  essential  differ- 
ences. Chronic  malaria  implies  a  supply  of  vital  resistance 
equal  to  the  demand;  malarial  cachexia  denotes  an  exhaustion 
of  this  supply.  Chronic  malaria  is  an  antagonistic  equilibrium 
between  parasite  and  host;  cachexia,  a  rupture  of  equilibrium. 
Chronic  malaria  is  a  conflict,  cachexia  a  conquest.  The  rela- 
tion between  chronic  malaria  and  cachexia  has  been  fitly 
compared  to  that  existing  between  a  compensated  heart  lesion 
and  broken  compensation.  Chronic  malaria  is  an  active  form 
of  malaria;  cachexia  is  a  sequel.  Cachexia  being  a  sequel, 
usually  of  chronic  malaria,  it  may  be  difficult  to  say  where  the 
influence  of  the  latter  ends  and  the  former  begins.  On  the 
other  hand,  it  is  frequently  difficult  or  impossible  to  differentiate 
between  a  relapse  in  chronic  malaria  and  a  reinfection. 

For  convenience  of  study,  chronic  malaria  may  be  divided 
into  a  latent  or  passive  stage  and  an  active  stage  or  stage  of 
relapse. 


I20  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

It  is  more  frequently  observed  in  children.  It  has  already 
been  shown  that  the  frequency  with  which  children  native  to 
the  soil  are  infected  constitutes  the  true  endemic  index  of  a 
locality. 

Chronic  malaria  may  be  due  to  one  infection,  but,  occurring 
chiefly  in  regions  where  repeated  reinfection  is  possible,  it  is 
highly  probable  that  reinfection  is  an  important  factor. 

An  analysis  by  me  of  a  large  number  of  cases  shows  the  follow- 
ing results :  Quartan  and  tertian  infections  are  more  prone  to 
relapse  than  estivo-autumnal.  The  percentage  of  relapses  to 
total  number  of  cases  of  quartan,  tertian,  and  estivo-autumnal 
is,  respectively,  65,  55,  and  45.  The  pertinacity  of  quartan 
may  be  regarded  as  a  conservative  effort  of  nature  to  perpetuate 
the  species.  It  is,  indeed,  remarkable  how  this  form  of  the 
parasite  is  conserved  in  certain  places  where  it  is  so  very  rare. 
However,  the  greatest  tendency  to  relapse  shown  by  the  benign 
infections  is  more  than  counterbalanced  by  the  severity  of  the 
symptoms  of  the  estivo-autumnal  relapses.  Hence  it  is  un- 
doubtedly true  that  the  estivo-autumnal  parasites  are  the  most 
important  factors  in  chronic  malaria. 

It  is  the  parthenogenetic  cycle  of  the  parasite  that  is  chiefly 
concerned  in  the  pathogenesis  of  chronic  malaria,  though  the 
asexual  forms  also  have  a  role.  The  parthenogametes  are  the 
parasites  of  the  latent  stage,  the  schizonts  of  the  active  stage. 
Parthenogenesis  is  the  bridge  across  the  gap  caused  by  interrup- 
tion of  the  schizogonic  cycle. 

The  most  frequent  course  is  for  chronic  malaria  to  follow  one 
or  more  acute  attacks.  In  some  instances,  however,  the  latent 
stage  may  precede  the  active.  Thus  it  is  not  extremely  rare 
to  meet  cases  with  evidences  of  chronic  malaria  which  have  no 
history  of  active  manifestations. 

The  latent  stage  of  chronic  malaria  resembles  in  some 
respects  a  period  of  incubation;  in  fact,  the  cases  reported 
with  unduly  long  stages  of  incubation  are  doubtless  nothing 
but  latent  stages  of  the  chronic  disease.  During  the  latent 
stage  parasites  may  or  may  not  be  found  in  the  peripheral 
blood. 

Symptoms  during  the  latent  stage  may  be  altogether  absent, 


in  which  case  latency  is  absolute,  or  there  may  be  present  cer- 
tain symptoms,  subjectively  insignificant,  constituting  relative 
latency.  These  symptoms  are  ordinarily  similar  to  the  pro- 
dromata  of  acute  malaria:  malaise,  loss  of  appetite,  aching  of 
the  back  and  legs,  digestive  disorders,  etc.,  together  with  anemia 
and  enlarged  spleen.  Latent  malaria  is  the  source  of  very  nu- 
merous infections,  and  is  of  the  utmost  importance  from  the 
viewpoint  of  prophylaxis. 

The  duration  of  latency  is  exceedingly  variable.  Relapses 
occur  at  shorter  or  at  longer  intervals. 

Relapses  at  short  intervals  have  been  recognized  since  the 
time  of  Hippocrates.  Later  the  septenary  periods  were  noted 
for  a  tendency  to  show  relapses,  and  this  idea  is  still  largely 
prevalent  among  the  laity.  This  shorter  interval  of  latency 
corresponds  more  or  less  closely  to  the  sexual  cycle  of  the  para- 
site and  to  the  period  of  incubation.  It  is  also  in  harmony  with 
the  law  of  Treille^"  and  with  the  studies  of  Cohen*"^  upon 
the  period  of  freedom  from  paroxysms  following  a  single  injec- 
tion of  quinine.  The  duration  of  this  period  is  from  five  to 
twenty-one  days,  of tenest  from  five  to  ten.  Relapses  at  shorter 
intervals  occasionally  exhibit  a  striking  periodicity. 

Relapses  at  longer  intervals  occur  at  from  one  to  twelve 
months,  exceptionally  longer.  Very  long  periods  of  freedom 
have  been  recorded,  even  up  to  sixty  years. ""^  Undoubtedly 
many  of  these  are  errors,  due  either  to  mistaken  diagnosis  or 
to  the  occurrence  in  the  interval  of  unrecognized  or  masked 
paroxysms.  However,  periods  as  long  as  three  years  have  been 
reliably  recorded. ^^ 

It  being  clinically  impossible  to  distinguish  between  a  relapse 
and  a  reinfection,  I  have  adopted  CelH's^=^  rule,  it  being  equally 
adapted  to  the  seasonal  prevalence  of  malaria  in  this  country. 
This  authority  regards  as  a  relapse  every  case  of  fever  which 
repeats  itself  in  the  same  individual  during  the  epidemic  year 
of  malaria,  from  July  of  one  year  to  the  end  of  the  following 
June.  It  is  true  that  this  may  include  some  cases  of  reinfection, 
but  it  is  unquestionably  the  most  practical  guide  and  eliminates 
a  maximum  of  error. 

It  is  ordinarily  the  relapse  that  brings  the  chronic  malarial 


122  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

to  the  physician.  The  relapse  may  consist  of  one  or  more  typic 
malarial  paroxysms  or  they  may  be  atypic.  Very  often  the 
first  stage  of  the  paroxysm  is  wanting.  They  may  exhibit 
quotidian,  tertian,  or  quartan  periodicity,  or  may  be  altogether 
irregular.  The  patient  usually  has  an  anemic  tint  and  may,  in 
advanced  cases,  be  jaundiced.  Occasionally  the  complexion 
may  be  earthy,  at  other  times  bronzed.  The  skin  is  dry  and 
often  scaly.  The  eyes  may  be  deep  set;  they  often  bear  a 
haggard,  restless  expression.  The  patient  appears  aged  beyond 
his  years.  The  condition  of  nourishment  is  poor,  and  there 
may  be  edema  of  the  face  and  feet.  There  are  weakness  of 
arms  and  legs  and  an  indisposition  to  physical  exertion.  The 
pulse  is  accelerated,  weak  and  sometimes  irregular.  Percus- 
sion may  reveal  an  increase  in  the  cardiac  dulness,  and  ausculta- 
tion an  anemic  murmur.  Dyspnea  on  slight  exertion,  a  feeling 
of  weight  or  pain  in  the  precordia,  and  palpitation  are  not 
infrequent  symptoms. 

The  extent  of  the  blood  destruction  depends  upon  the  severity 
and  proximity  of  the  paroxysms  and  the  activity  of  the  blood- 
making  organs.  The  number  of  red  cells  frequently  falls  to 
one  million  per  cubic  millimeter  or  even  less.  In  other  cases 
the  destroyed  cells  are  nearly  replaced  within  a  short  time  after 
the  relapse.  The  hemoglobin  percentage  is  sometimes  dis- 
proportionately lower  than  the  red  cell  count,  though  occasion- 
ally it  may  be  normal  or  above.  The  leucocyte  formula  is 
similar  to  that  of  acute  infections.  Parasites  of  the  asexual 
cycle  are  usually  found  in  the  peripheral  blood.  Tertian 
gametes  are  frequently  seen,  while  quartan  are  rare.  The 
frequency  of  crescents  and  ovoids  is  very  variable.  In  my 
experience  they  are  not  often  seen  in  blood  obtained  from  the 
superficial  circulation.  They  are  also  infrequent  in  the  experi- 
ence of  some  other  observers.  The  majority  of  writers,  how- 
ever, have  seen  estivo-autumnal  gametes  in  a  considerable 
proportion  of  their  cases. 

Other  blood  changes,  as  nucleated  red  cells,  microcytes, 
macrocytes,  and  poikilocytes,  are  more  common  in  chronic 
than  in  acute  malaria. 

The  respiration  is  usually  quickened,  especially  after  exercise. 


MALARIA  123 

Chronic  bronchial  catarrh,  usually  of  a  mild  degree,  is  not  a  rare 
condition  in  chronic  malaria,  and  epistaxis  is  sometimes  profuse. 

Digestive  disorders  are  very  common  and  marked  meteorism 
may  exist.  The  condition  of  the  bowels  is  not  constant,  diar- 
rhea sometimes  alternating  with  constipation.  Dysenteric 
manifestations  are  frequent. 

The  spleen  may  be  of  normal  proportions  in  mild  cases,  but 
is  usually  enlarged,  sometimes  enormously  so,  passing  the 
median  line  of  the  abdomen  and  the  iliac  crest.  It  may  or  may 
not  be  tender  or  painful;  in  the  former  case  the  pain  is  usually 
of  a  pulling  nature  and  referred  to  the  left  shoulder.  If 
perisplenitis  with  adhesions  does  not  occur,  the  spleen  may  be 
movable  or  floating.  Often  the  spleen  enlarges  during  the 
active  stage  to  recede  slowly  during  latency.  The  liver  is  often 
sHghtly  enlarged  and  tender. 

Headache,  nervousness,  restlessness,  vertigo,  insomnia,  and, 
in  severe  cases,  impaired  memory,  are  observed.  The  urine  is 
often  albuminous. 

Masked  Malaria. — Masked  or  larvate  malaria,  like  pernicious 
malaria,  needs  complete  overhauling.  Nearly  every  disease  in 
the  category  has  been  confounded  with  malaria  and  classed  as 
larvate.  This  heterogeneous  group  has  been  expanded  to 
embrace  diseases  unrelated  in  any  way  to  malaria,  diseases 
complicating  malaria,  and  symptoms  and  sequelae  of  malaria. 
The  frequency  of  masked  malaria  varies  inversely  with  the  care 
employed  in  diagnosis.  Masked  malaria  is  merely  atypic  ma- 
laria. The  symptoms  being  of  little  value  in  diagnosis,  this 
must  be  made  by  the  anamnesis,  the  microscopic  examina- 
tion of  the  blood,  and  by  the  therapeutic  test.  Nervous,  gastro- 
intestinal, and  cutaneous  disorders  are  those  most  frequently 
recorded  as  masked.  Most  of  these  are  to  be  considered 
under  Complications  and  Sequelee. 

COMPLICATIONS  AND  SEQUEL.^ 

Circulatory  System. — Malaria  is  very  frequently  comphcated 
by  heart  disorders.  In  the  negro  population  of  the  South, 
in  whom  syphihs,  abuse  of  alcohol  and  tobacco,  pneumonia, 


124  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

and  other  etiologic  factors  are  very  prevalent,  lesions  of  the 
circulatory  system,  particularly  valvular  lesions  of  the  heart, 
often  add  to  the  gravity  of  severe  malarial  infections.  These 
are  to  be  regarded  almost  invariably  as  complications  and  not 
as  sequelae.  Circulatory  lesions,  the  direct  result  of  malarial 
invasion,  are  remarkably  rare.  Many  such  cases  were  reported 
before  the  discovery  of  the  parasite,  but  are  for  this  reason 
practically  valueless. 

Probably  the  commonest  cardiac  sequel  of  malaria  is  myo- 
carditis. Slight  evidences  of  degeneration  of  the  heart  muscle 
are  sometimes  found  after  death  in  cases  which  presented  no 
symptoms  during  life. 

Angina  pectoris  is  occasionally  observed  in  connection  with 
malaria.  It  may  exist  as  a  complication  or  as  the  cardialgic 
type  of  pernicious  malaria. 

Much  was  formerly  written  about  malarial  endocarditis, 
aortitis,  and  endarteritis.  These  occur  but  rarely  and  only  as 
complications.  Pericarditis  and  aortic  aneurism  are  usually 
complications.  Phlebitis  and  thrombosis  have  been  seen, 
more  often  in  cases  of  cachexia. 

There  is  absolutely  no  evidence  that  malaria  is  a  causative 
factor  in  either  lymphangitis  or  lymphadenitis,  the  so-called 
malarial  bubo,  these  conditions  occurring  only  as  complications. 
A  suppurating  bubo,  like  other  septic  processes,  may  be  ac- 
companied by  an  intermittent  temperature. 

Respiratory  System. — Coryza  may  occur  as  a  complication 
to  malaria,  especially  during  unseasonable  weather.  Bron- 
chitis is  a  common  complication,  during  a  portion  of  the  malarial 
season  occurring  with  marked  frequency.  It  is  observed  oftener 
in  the  negro  than  in  the  white  race.  Subacute  or  chronic 
bronchitis  is  usual  in  chronic  malaria  and  cachexia. 

A  peculiar  condition  of  the  pulmonary  apices  has  been  de- 
scribed. It  consists  of  a  rapid  and  transient  congestion  of  the 
apex  of  one  or  both  lungs,  arising  and  disappearing  with  the 
paroxysm.  The  cough  is  dry  and  painful,  the  expectoration 
is  scanty,  occasionally  bloody,  and  there  may  be  bronchial 
breathing  and  increased  vocal  fremitus.  I  have  had  no  experi- 
ence with  this  complication. 


MALARIA  125 

Pneumonia  was  long  considered  a  manifestation  or  a  sequel 
of  malaria,  but  it  is  now  known  that  they  are  entirely  distinct 
diseases. 

Gastro-intestinal  Tract. — Stomatitis  is  sometimes  observed 
in  malaria.  Parotitis  is  an  infrequent  complication.  Dyspeptic 
symptoms  denoting  chronic  gastric  catarrh  are  not  uncommon 
in  cases  of  chronic  malaria  and  cachexia.  Gastric  ulcer  in 
association  with  amyloid  changes  in  the  mucosa  is  rarely  noted. 
Hematemesis  occasionally  assumes  alarming  proportions. 

Enteritis  is  a  much  more  frequent  sequela  of  malaria  than 
ordinarily  regarded.  The  inflammation  may  advance  to  ul- 
ceration. The  process  has  been  frequently  demonstrated  by 
autopsies  to  be  due  to  accumulations  of  parasites  in  the  intes- 
tinal mucosa.  Diarrhea  is  common,  especially  in  persons 
improperly  fed.  Profuse  hemorrhage  occasionally  occurs,  in 
which  case  the  microscopic  examination  of  the  blood  is  of  the 
greatest  value  in  differentiating  the  disease  from  typhoid  fever. 

Dysenteric  symptoms  arising  in  the  course  of  malaria  and 
the  dysenteric  form  of  pernicious  malaria  have  been  considered. 
Well-marked  dysentery  may  be  present  either  as  a  complica- 
tion or  as  a  sequela.  Often  the  dysenteric  symptoms  pre- 
dominate, thus  constituting  one  of  the  commonest  forms  of 
masked  malaria. 

Besides  the  ameba,  other  intestinal  parasites  may  complicate 
paludism.  Of  these  by  far  the  most  common  is  the  Ascaris 
lumbricoides.  Uncinariasis  is  not  an  infrequent  complication 
in  some  sections.  I  have  observed  an  infection  with  Hymen- 
lepis  nana  associated  with  malaria.  It  is  not  improbable  that 
intestinal  helminthiasis  aggravates  the  anemia  and  the  gastro- 
intestinal and  nervous  symptoms.  In  examining  the  blood  for 
the  malaria  parasite  the  presence  of  eosinophilia  calls  for  an 
examination  of  the  feces. 

Cirrhosis  of  the  liver  the  direct  result  of  malarial  infection, 
described  as  relatively  frequent  in  certain  portions  of  the  tropics, 
appears  to  be  rare  in  this  section.  Hypertrophic  hepatitis  may 
result  from  prolonged  infection.  Ascites  occasionally  develops, 
particularly  in  chronic  malaria  and  cachexia. 

The   Blood   and    Spleen. — Leukemia    follows   malaria   only 


126  ENDEMIC   DISEASES    OF    THE    SOUTHERN    STATES 

rarely,  probably  never  as  a  true  sequela,  though  many  cases 
of  leukemia  give  a  history  of  past  malaria. 

The  relation  of  splenic  anemia  to  malaria  is  not  clear. 
Splenic  anemia  may  come  into  consideration  in  differential 
diagnosis. 

Malarial  Cachexia. — In  this  condition  the  parasites  have 
obtained  undisputed  possession  of  the  host.  The  defensive 
forces  have  been  completely  conquered,  the  blood-making 
organs  can  no  longer  meet  the  demand .  made  upon  them, 
and  toxins,  unopposed,  work  changes,  often  irreparable,  in 
important  organs.  Cachexia  has  been  classified  as  dry  or 
humid,  according  to  the  absence  or  presence  of  anasarca,  and 
as  acute  or  chronic.  Acute  cachexia  is  characterized  by  a  rapid 
onset  and  development  of  symptoms  and  usually  follows  acute 
malaria,  occasionally  after  only  one  or  two  attacks.  These 
cases  are  infrequent.  Chronic  cachexia,  the  usual  form,  is  a 
sequela  of  chronic  malaria. 

Malarial  cachexia  is  found  where  the  severe  forms  of  malaria 
are  endemic.  It  may  be  stated  as  a  general  ryle  that  the  fre- 
quency of  cachexia  among  the  white  race  is  an  index  to  the  preva- 
lence of  grave  infections.  It  is  much  more  common  in  the 
white  race  than  in  the  negro.  While  negro  children  are  not 
infrequently  the  subjects  of  malarial  cachexia,  it  is  much  rarer 
in  the  adult  negro.  Of  adults,  males  are  more  commonly 
cachectic  than  females;  among  children  the  proportion  is  about 
even.  The  condition  rarely  develops  in  persons  of  the  better 
class,  but  is  seen  in  those  living  under  improper  hygienic  con- 
ditions and  who  neglect  the  treatment  of  acute  malaria. 

Cases  of  cachexia  developing  without  outbreaks  of  malaria 
have  been  reported,  but  are  subject  to  question.  Infections 
with  the  estivo-autumnal  parasites  are  followed  by  cachexia 
much  more  frequently  than  tertian  and  quartan  infections. 

The  cachectic  usually  presents  a  singular  appearance.  The 
emaciated  limbs  are  in  marked  contrast  to  the  big  belly,  and 
the  features  are  aged  beyond  the  years.  The  most  pronounced 
phenomena  are  the  anemia  and  the  enlarged  spleen.  The  red 
blood-cells  may  be  reduced  to  seven  or  eight  hundred  thousand 
per  cubic  millimeter.     The  leucocytes  are  generally  normal  in 


128  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

number  or  a  little  below.  Numerous  differential  counts  have 
shown  a  relative  increase  of  the  large  mononuclear  elements. 
The  red  cells  may  show  basophile  degeneration,  polychromato- 
philia,  poikilocytosis  and  nuclei,  but  none  of  these  changes  are 
by  any  means  constant.  According  to  my  experience  parasites 
are  rarely  found  in  the  peripheral  blood.  The  spleen  often 
extends  to  the  umbilicus  and  to  the  crest  of  the  ilium,  sometimes 
beyond.  It  is  usually  hard  and  the  anterior  border  presents 
a  sharp  edge.  Pain  and  tenderness  on  pressure  are  not  always 
felt.  Occasionally  a  bruit  is  to  be  detected  over  the  splenic 
area. 

The  pulse  is  small,  compressible,  and  may  be  irregular. 
Palpitation  of  the  heart  and  hemorrhages,  especialty  epistaxis, 
ma}'  occur.  An  anemic  murmur  over  the  precordia  is  often 
heard.  Myocarditis  and  dilatation  are  not  infrequent.  The 
breath  is  short,  sometimes  amounting  to  actual  dyspnea.  A 
cough  is  common  and  signs  of  bronchitis  may  be  elicited.  Pul- 
monary edema  is  a  late  symptom. 

The  temperature  may  be  normal  or  subnormal  for  long 
periods,  though  evening  rises  are  often  observed.  Typic  par- 
oxysms are  not  frequent.  Fever  often  follows  imprudences. 
Whether  the  fever  of  cachexia  is  due  directly  to  parasitic  activ- 
ity or  to  organic  changes  is  not  definitely  known.  The  appetite 
is  generally  poor  and  the  digestion  tardy.  Epigastric  pain, 
nausea,  and  vomiting  may  be  complained  of.  The  tongue  and 
oral  mucous  membrane  are  pale.  Diarrhea  and  dysentery  fre- 
quently occur.  Meteorism  is  common.  The  liver  is  usually 
somewhat  enlarged  at  first;  later  it  may  become  atrophic. 
Ascites  is  not  a  rare  manifestation.  When  fever  exists  the 
urine  is  ordinarily  scanty  and  highly  colored.  Delayed  develop- 
ment of  the  genitals  is  common  in  the  young,  and  diminished 
sexual  power  is  not  rare  in  the  adult.  Indifference,  intellectual 
torpor,  somnolence,  headache,  and  vertigo  are  observed  in 
cachectics.  Resistance  to  cold  is  lessened  and  rheumatic  pains 
are  experienced.  The  skin  is  pallid,  dry,  and  rough,  and  may 
exhibit  sores  or  purpuric  spots.     Anasarca  may  supervene. 

Pneumonia,  dysentery,  hemoglobinuric  fever,  and  nephritis 
are  common  complications  of  cachexia,  and  amyloid  degenera- 
tion, especially  of  the  kidneys,  an  occasional  sequela.  Peri- 
splenitis occasionally  occurs  and  may  be  the  cause  of  severe 


MALARIA  129 

pain,  especially  if  adhesions  take  place.  A  heavy  spleen  may 
cause  relaxation  of  its  supports  and  become  "floating"  or 
"wandering."  This  condition  is  seen  more  often  in  multi- 
parous  females.  By  pressure  on  neighboring  organs  a  wander- 
ing spleen  may  cause  pain,  digestive  disorders,  or  even  intestinal 
occlusion.     The  pedicle  may  become  twisted. 

Rupture  of  the  spleen  is  an  infrequent  complication  of  mala- 
rial cachexia.  It  is  very  rarely  associated  with  acute  malaria.  I 
observed  a  case  in  a  subject  of  cachexia  who  had  a  large,  hard 
spleen.  Recovery  followed,  notwithstanding  extensive  hemor- 
rhage. The  symptoms  of  rupture  of  the  spleen  consist  of 
violent  pain  in  the  splenic  region  referred  to  the  left  shoulder, 
together  with  evidences  of  shock  and  hemorrhage.  The  mor- 
tality of  cases  not  treated  with  splenectomy  is  exceedingly 
high.     Death  may  occur  in  from  a  few  hours  to  five  days. 

Abscess  of  the  spleen  is  a  rarer  complication  of  malaria  even 
than  rupture.  I  am  able  to  collect  from  the  literature  mention 
of  not  more  than  fifty  cases.  The  common  pyogenic  cocci  and 
the  bacillus  coli  communis  are  the  bacteria  usually  present  in 
splenic  abscesses.  The  symptoms  are  sometimes  as  vague  as 
those  of  abscess  of  the  liver.  There  may  be  pain  in  the  left 
hypochondrium,  especially  if  the  abscess  is  superficial  and  the 
peritoneum  is  involved.  The  pain  is  often  referred  to  the  left 
shoulder.  Pain  may,  however,  be  entirely  wanting.  The 
temperature  is  usually  elevated,  though  in  rare  instances  it 
may  be  normal  or  subnormal.  It  is  usually  intermittent  and 
associated  with  chills  and  sweats.  Emaciation  may  be  extreme, 
notwithstanding  the  appetite  is  sometimes  voracious.  Abscess 
of  the  spleen  may  be  confused  with  uncomplicated  malaria 
and  renal,  gastric,  or  pancreatic  disease.  The  presence  of 
leucocytosis  and  the  therapeutic  tests  are  valuable  diagnostic 
points.  Signorelli's  spleen  point  may  be  a  useful  guide.  This 
is  a  painful  area  corresponding  to  the  fifth  intercostal  space  near 
the  left  nipple.  Without  operation  the  prognosis  is  very  grave; 
with  timely  incision  and  drainage  a  considerable  per  cent, 
recover. 

Infarcts  and  gangrene  of  the  spleen  are  noted  among  the 
rare  complications  of  the  spleen  in  malarial  cachexia. 
9 


130  ENDEMIC    DISEASES    OE    THE    SOUTHERN    STATES 

Genito-urinary  Organs.  Nephritis. — The  frequency  of  neph- 
ritis recorded  as  a  sequela  of  malaria  varies  greatly  with 
locality,'  type  of  fever,  and  with  the  idea  of  what  constitutes 
nephritis.  The  real  frequency  of  nephritis  in  malaria  is  in 
about  },-2  to  2  per  cent,  of  the  cases  of  tertian  and  quartan  in- 
fections and  2  to  5  per  cent,  in  estivo-autuninal.  The  negro  is 
apparently  more  susceptible  to  the  renal  lesions  of  malaria 
than  is  the  white.  More  cases  are  seen  in  the  months  during 
which  the  estivo-autumnal  fevers  prevail.  The  middle  aged 
and  the  old  are  less  often  attacked  than  the  young.  Nephritis 
is  much  more  prone  to  result  from  chronic  than  from  acute 
malaria.  The  nephritis  is  most  often  acute,  but  it  is  highly 
probable  that  malaria  is  an  important  factor  in  the  etiology  of 
chronic  nephritis.  Chronic  nephritis  may  follow  the  acute 
form  or  may  exist  as  such  from  the  beginning.  True  hemor- 
rhagic nephritis  is  rare.  There  is  ordinarily  nothing  character- 
istic either  in  the  symptoms  or  pathologic  histology  of  the 
nephritis  of  malaria.  Amyloid  degeneration  is  a  renal  sequela 
of  malaria. 

Occasionally  intense  lumbar  pain,  closely  simulating  renal 
colic,  is  experienced  as  a  complication  of  malaria.  This  colic 
usually  responds  promptly  to  quinine,  though  the  pathogenesis 
is  not  clear. 

Forms  of  orchitis  and  epididymitis  have  for  a  long  time  been 
attributed  to  malaria.  Either  may  complicate  malaria.  I 
have  seen  several  cases  of  epididymitis  associated  with  malaria, 
there  being,  however,  in  each  case  a  history  of  venereal  disease. 
There  is  at  the  present  time  absolutely  no  evidence  that  either 
orchitis  or  epididymitis  is  ever  a  true  sequela  of  malarial  dis- 
ease. The  same  may  be  said  of  hydrocele,  which  some 
observers  have  ascribed  to  malaria. 

It  is  doubtful  whether  genuine  atrophy  of  the  testicles  ever 
occurs  as  the  result  of  malaria.  It  is  more  probable  that  these 
cases  are  due  to  improper  development,  the  result  of  cachexia, 
climate,  or  other  factors.  Metrorrhagia  and,  more  often, 
menorrhagia  and  amenorrhea  are  not  infrequently  seen  with 
malaria.     Sterility  has  been  charged  to  paludism. 

It  was  formerly  beheved  that  pregnancy  conferred  a  degree  of 


MALARIA  131 

immunity  against  malaria.  This  is  now  known  not  to  be  true. 
If  the  pregnant  woman  is  attacked  less  often  with  malaria  it  is 
because  she  is  less  often  exposed  to  infection,  and  not  on  account 
of  an  immunity  which  pregnancy  confers  upon  her. 

A  list  of  cases  is  appended  to  give  an  idea  of  the  frequency  with 
which  abortion  and  premature  labor  occur  as  the  result  of 
malaria  compHcating  pregnancy.  The  first  column  of  figures 
records  the  number  of  cases  in  which  the  complication  appeared; 
the  second  column  shows  the  number  of  abortions  and  prema- 
ture labors  which  occurred : 

Pascali*'^ 34  25 

Weatherly,"  in  India 88  28 

Weatherly,"  in  England 58  2 

Weatherly,"  in  Africa 97  22 

Weatherly,"in  Florida 52  22 

Hospital,  Rome^^ 51  33 

Lwow*'" 26  10 

Goth^" 46  19 

Bonfils^^i^ 105  73 

Williams*" 15 

572  234 

24.4  per  cent. 

This  percentage  is  at  least  twice  as  large  as  that  resulting 
from  my  experience. 

I  am  inclined  to  believe  that  the  negro  is  much  less  Uable  to 
suffer  abortion  or  premature  delivery  than  is  the  white.  This  is 
in  keeping  with  the  well-known  relative  immunity  of  the  negro 
to  some  of  the  effects  of  malaria. 

Cases  accompanied  by  continued  high  temperature,  retching, 
and  vomiting,  and  which  are  more  resistant  to  treatment,  are 
those  in  which  abortion  most  frequently  occurs.  Hence  it 
follows  that  abortion  is  more  often  due  to  estivo-autumnal 
fever  than  to  tertian  and  quartan,  and  to  multiple  infections 
than  to  single. 

The  danger  of  abortion  and  premature  delivery  is  greater  in 
proportion  as  the  pregnancy  is  advanced. 

The  factors  in  the  interruption  of  pregnancy  are  probably 
fever,  retching,  vomiting,  anemia,  and  toxins.  It  is  not  im- 
probable that  in  some  cases  parasitic  localizations  in  the  uterine 


132  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

vessels  excite  pains  or  cause  placental  separation,  though  for 
this  theory  there  is  as  yet  no  pathologic  proof. 

If  the  malarial  infection  does  not  terminate  the  pregnancy  the 
labor  at  full  term  is  apt  to  be  slow,  especially  the  first  stage. 

Children  born  at  full  term  of  malarial  mothers  are  apt  to 
be  smaller  and  lighter  than  normal,  and  the  mortality  is 
higher. 

Labor  often  rekindles  latent  malaria,  which,  in  thepuerperium, 
is  not  infrequently  atypic,  the  first  or  third  stages  of  the  par- 
oxysm or  complete  intermission  of  the  temperature  sometimes 
lacking.  Subinvolution,  postpartum  hemorrhage,  and  sup- 
pression of  milk  may  occur  with  puerperal  malaria. 

Nervous  System. — It  is  often  impossible  to  determine  whether 
nervous  manifestations  in  malaria  are  complications  or  sequelae. 
It  is  certain  that  many  cases  reported  as  due  to  malaria  are 
purely  complications.  This  is  the  case  with  multiple  neuritis, 
of  which  numerous  cases  have  been  ascribed  to  malaria.  In  by 
far  the  majority  of  cases  the  existence  of  malaria  was  not  estab- 
lished by  blood  examination;  in  others  it  is  not  certain  that 
the  neuritis  was  due  to  malaria. 

Neuritis  occurring  during  and  after  malarial  disease  has  often 
been  described.  Paraplegia  and  symptoms  resembling  multiple 
sclerosis  are  also  occasionally  observed. 

Hemiplegia,  paraplegia,  and  various  monoplegias,  either  with 
or  without  aphasia  or  sensory  disturbances,  are  not  infrequently 
associated  with  malaria. 

Cerebellar  syndromes  are  rarely  observed  in  malaria.  They 
consist  of  general  weakness,  rigidity,  and  pain  in  the  back  of  the 
neck,  intense  headache,  ataxic  gait  with  a  tendency  to  fall 
backward  and  to  the  left,  tremors,  incoordination  of  movement, 
dysarthria,  nystagmus,  and  vomiting.  The  tertian  parasite  is 
usually  present  in  these  cases. 

Bulbar  symptoms  are  occasionally  encountered.  Such  are 
hypoglossal  and  facial  paralysis,  ataxia  of  arm,  dysarthria  or 
anarthria,  and  staggering  gait.  These  symptoms  are  usually 
obstinate. 

Various  psychoses  occur  in  connection  with  malaria,  either 
during  or  following  acute  or  chronic  malaria.     The  commonest 


MALARIA  133 

of  these  disorders  are  weakened  memory,  melancholia,  mania 
and  delusional  insanity.  Suicidal  and  erotic  tendencies  may 
be  observed. 

Hysteria  is  not  a  rare  phenomenon  during  paludism.  It  is 
probably  the  result  of  anemia  in  predisposed  persons.  As  it 
may  assume  any  of  a  multitude  of  forms,  its  chief  significance  is 
from  the  viewpoint  of  diagnosis. 

A  mild  neurasthenia  is  probably  due  directly  to  malaria  in 
some  instances,  and  preexisting  neurasthenia  is  often  aggravated 
by  malarial  infection.  The  usual  symptoms  are  restlessness, 
nervousness,  insomnia,  and  annoying  distinctness  of  the  heart 
beat  on  retiring. 

It  was  formerly  believed  that  intercurrent  malaria  exercised 
a  beneficial  influence  upon  epilepsy.  So  far  from  this  being 
the  case,  however,  epilepsy  is  frequently  aggravated  by  paludal 
infection. 

Violent  choreic  symptoms  are  among  the  rare  nervous 
phenomena. 

The  Eye. — Injection  of  the  conjunctiva  is  not  infrequently  , 
associated  with  neuralgia  of  the  fifth  nerve.  True  intermittent 
conjunctivitis  occurs  but  rarely  if  at  all.  Both  interstitial  and 
dendritic  keratitis  are  occasionally  observed  with  malaria, 
though  it  is  doubtful  whether  either  form  can  be  attributed  to 
malaria.  The  same  probably  holds  true  for  vesicular  keratitis 
or  the  so-called  corneal  herpes.  In  pernicious  seizures  with 
coma-vigil  the  eyes  are  more  or  less  exposed  to  damage. 

Iritis  exists  as  a  complication  of  malaria  in  rare  instances. 
Choroiditis  occasionally  occurs  in  connection  with  retinitis. 
Optic  neuritis  is  observed  chieiiy  in  cachectics.  In  the  majority 
of  cases  it  proceeds  to  atrophy. 

Retinal  hemorrhages  are  oftenest  minute  and  located  far 
forward,  hence  they  may  be  easily  overlooked.  Occasionally, 
however,  they  are  peripapillary  or  macular  and  of  large  size; 
in  the  latter  case  the  prognosis  is  more  serious.  Persistent 
or  periodic  amaurosis  without  evident  retinal  changes'  is  some- 
times seen.  I  have  seen  one  case  of  hemianopia  following 
pernicious  malaria  of  the  comatose  form  which  terminated  in 
complete  restoration  of  vision.     Rarer  optic  manifestations  oc- 


134  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

curring  in  conjunction  with  malaria  are  hemorrhage  and  infiltra- 
tion into  the  vitreous  humor. 

The  Ear. — Otalgia,  labyrinthine  vertigo,  otitis  media,  and 
lesions  of  the  internal  ear  and  auditory  nerve  have  been  de- 
scribed as  occurring  with  malaria,  but  in  no  case  has  the  blood 
been  examined. 

The  senses  of  taste  and  smell  are  said  to  be  diminished  or 
abolished  in  rare  cases  of  malaria. 

The  Skin. — The  frequency  with  which  herpes  occurs  in 
malaria  has  already  been  mentioned.  Next  to  herpes,  urticaria 
is  the  most  frequent  cutaneous  lesion  associated  with  malaria. 
The  possibility  of  the  eruption  being  caused  by  quinine  should 
be  remembered.  Erythema  is  not  an  uncommon  eruption  with 
malaria,  and  may  simulate  the  eruption  of  scarlatina.  Pruritus 
may  be  present.  Erythema  nodosum  has  occasionally  been 
observed.  Petechiae  and  large  purpuric  spots  are  not  rare  in 
subjects  of  chronic  malaria  and  of  cachexia.  In  these  patients 
ulcers  and  furunculosis  may  exist  as  complications. 

The  occurrence  of  herpes  zoster  in  malaria  is  very  variable. 
In  6i6  cases  of  malaria  studied  by  Thayer  and  Hewetson'*'^ 
herpes  zoster  occurred  only  once,  and  this  complication  existed 
but  once  in  1,780  cases  of  malaria  reviewed  by  Anders.''"^ 
On  the  other  hand,  Winfield"^'*  found  malarial  parasites  in  the 
blood  of  14  out  of  25  cases  of  herpes  zoster.  I  have  recently 
observed  g  cases  of  herpes  zoster.  In  3  the  blood  examined 
revealed  estivo-autumnal  parasties;  in  2  there  was  a  history  of 
recent  malaria  and  the  examination  of  the  blood  was  negative. 

As  previously  mentioned,  purpura  simplex  is  not  an  uncom- 
mon occurrence  in  malaria.  Purpuric  eruptions  may  also,  but 
rarely,  be  noted  in  hemoglobinuric  fever.  But  true  purpura 
hemorrhagica  is  very  rarely  seen  in  malaria.  About  seven  cases 
are  recorded,  one  of  which  I  observed  in  the  South. 

Malaria  undoubtedly  predisposes  to  the  development  of 
gangrene,  especially  when  it  has  become  chronic  or  has  advanced 
to  cachexia.  More  than  this,  however,  cannot  be  said  of  the 
part  played  by  malaria  in  the  etiology  of  gangrene.  Gangrene 
of  almost  every  part  of  the  surface  of  the  body  has  been  ob- 
served in  malarial  subjects.     The  gangrene  is  more  commonly 


MALARIA  135 

of  the  dry  variety.  Local  asphyxia  not  followed  by  gangrene 
occurs  also.  Raynaud's  disease,  or  symmetric  gangrene,  has 
been  thought  to  be  due  to  malaria  in  many  instances,  but  re- 
ports of  cases  in  which  the  malarial  parasite  was  present  in  the 
blood  are  still  rare. 

Other  Conditions  and  Diseases. — At  various  times  malaria 
has  been  supposed  to  predispose  to  certain  diseases.  Such  were 
typhoid  fever  and  diabetes.  It  has  also  been  thought  to  exert 
an  antagonistic  influence  toward  other  diseases,  as  tuberculosis, 
cancer,  and  influenza.  It  is  probable  that  any  predisposing 
power  on  the  part  of  malaria  to  other  diseases  is  only  indirect. 
It  is  a  priori  improbable  that  a  disease  conferring  only  relative 
immunity  toward  itself  should  immunize  against  or  antagonize 
other  diseases,  and  such  is  the  result  of  experience. 

Typhoid  Fever. — The  complication  of  typhoid  fever  with 
malaria  is  not  very  rare.  A  search  of  the  literature  reveals 
records  of  215  cases  in  which  the  presence  of  malaria  parasites 
and  the  typhoid  bacilli  or  the  Widal  reaction  conclusively 
proved  the  association. 

Typhoid  fever  is  more  frequently  compHcated  with  tertian 
than  with  estivo-autumnal  malaria.  Craig  has  reported  the 
only  case  of  simultaneous  typhoid  fever  and  quartan  malaria  of 
which  I  have  any  knowledge. 

Usually  the  malarial  symptoms  arise  and  the  parasites  are 
detected  during  convalescence  from  the  typhoid  fever,  though 
they  may  be  present  during  the  course  of  the  latter.  When  the 
onset  of  the  malaria  precedes  that  of  the  typhoid  fever,  the 
malarial  parasites  often  disappear  from  the  peripheral  circula- 
tion upon  the  advent  of  the  typhoid  fever,  sometimes  reappear- 
ing and  producing  symptoms  during  the  convalescence  from 
typhoid.  This  is  analogous  to  the  result  of  inoculating  a  given 
variety  of  malarial  parasites  into  a  malarial  patient  harboring  a 
different  form,  the  older  infection  usually  surrendering  Lo  the 
fresh.  Malaria  occurring  at  the  height  of  typhoid  fever  may  or 
may  not  modify  the  course  of  the  latter.  The  mortality  of  the 
compHcation  of  these  two  fevers  is  higher  than  that  of  uncom- 
plicated typhoid. 

The  term  "  typhomalarial  fever,"  if  used  at  all,  should  be 


136  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

restricted  to  those  cases  in  which  exact  methods  of  diagnosis 
prove  it  applicable.  However,  the  combination  of  typhoid  and 
malarial  fevers  is  no  more  entitled,  either  by  virtue  of  intimacy 
or  frequency,  to  a  hyphenated  appellation  than  is  tuberculosis 
or  gonorrhea  in  association  with  inalaria.  It  was  formerly 
believed  that  a  mysterious  fusion  of  both  diseases  produced  a 
hybrid  pathologic  entity.  It  is  now  definitely  known  that  this 
is  not  the  case.  Such  a  diagnosis  is  ordinarily  a  compromise 
based  on  a  lack  of  frankness  to  acknowledge  inability  to  diag- 
nose certain  cases  of  fever  in  the  earliest  stages,  and  is  not  only 
loose  and  unscientific,  but  is,  in  many  insta:nces,  actually  harm- 
ful, as  it  often  leads  to  the  abuse  of  purgatives  and  quinine. 
There  is  no  question  but  that  nearly  all  of  the  so-called  "typho- 
malaria"  is  pure  typhoid  fever. 

Diabetes. — This  is  undoubtedly  a  rare  complication.  I 
recall  the  case  of  a  diabetic,  passing  more  than  5  per  cent,  of 
sugar,  who  was  attacked  with  estivo-autumnal  malaria.  The 
latter  ran  an  uneventful  course  and  seemed  to  have  no  effect  on 
the  sugar  excretion.  The  patient  died  several  months  later  of 
bronchitis. 

Polyuria  in  malarial  subjects  has  already  been  mentioned. 

Tuberculosis. — In  the  South,  where  tuberculosis  is  very 
prevalent  in  the  negro  race,  the  negro  death  rate  from  tubercu- 
losis ranging  from  100  to  150  per  cent,  higher  than  in  the  white 
race,  tuberculosis  and  malaria  not  infrequently  concur,  espe- 
cially in  the  colored  race.  Malarial  cachexia  predisposes  to 
tuberculosis  only  in  a  slight  measure,  if  at  all.  The  negro,  who 
is  less  often  the  subject  of  cachexia  than  the  white,  more  often 
shows  the  combination  of  malaria  and  tuberculosis.  The 
malaria  may  prove  rapidly  fatal,  both  diseases  may  be  unmodi- 
fied in  their  progress,  or  the  tuberculosis  may  assume  a  more 
rapid  course.  The  old  idea  that  the  two  diseases  are  antagon- 
istic is  disproved  by  their  not  uncommon  occurrence  in  the 
same  individual,  as  I  have  frequently  observed. 

Influenza. — Anders"^  believes  that  there  exists  a  decided 
antagonism  between  malaria  and  influenza.  Simms  and  War- 
wick,**^" however,  mention  simultaneous  epidemics  of  malaria 
and  influenza  in  Alabama,  when, '  'of  those  infected  with  malaria, 


MALARIA  137 

60  per  cent,  were  brought  down  with  this  disease,  and  it  was 
much  more  severe  than  in  those  who  were  not  infected." 

Cancer. — Based  on  the  supposition  that  cancer  is  not  so  fre- 
quent in  tropic  latitudes,  and  on  the  report  of  Krzowitz,  in  1776, 
of  a  case  of  the  breast  healing  after  an  attack  of  double  tertian 
malaria,  Loeffler'"*  assumed  an  antagonsim  between  the  two 
diseases,  and  proposed  as  a  therapeutic  measure,  the  inocula- 
tion with  malaria  of  cancerous  patients.  A  few  experiments 
and  numerous  reports  of  cancer  among  tropic  people  and 
malarial  subjects  have  shown  the  absolute  uselessness  of  such 
a  procedure.  On  the  other  hand,  it  is  believed  that  malaria  of 
long  standing  predisposes  to  cancer  of  the  liver. 

Smallpox  is  an  infrequent  complication  of  malaria.  L  averan'^ 
observed  several  such  cases  in  Constantine.  The  malaria 
parasites  usually  disappear  from  the  blood  with  the  onset  of  the 
smallpox  where  the  onset  of  the  latter  succeeded  that  of  the 
former.  The  mortahty  of  these  cases  was  unusually  high. 
Pyemic  foci  and  hemorrhages  were  observed. 

Syphilis  is  a  common  complication  of  paludism.  Under  these 
circumstances  syphilis  is  more  rapid  in  its  course  and  is  rebellious 
to  treatment  in  proportion  to  the  chronicity  of  the  malarial 
infection.  In  malarial  cachectics  antisyphilitic  treatment  is 
sometimes  all  but  impotent.  Syphilitic  buboes  are  more  apt  to 
suppurate  and  become  ugly  indolent  ulcers.  Malarial  invasion 
may  arouse  latent  syphilis. 

Malaria  in  Children. — In  older  children  there  is  nothing  un- 
usual in  the  malarial  attacks.  In  infants  and  young  children 
there  are  several  points  which  deserve  a  brief  consideration. 

The  type  of  fever  is  more  often  quotidian,  sometimes  tertian 
or  double  quotidian,  rarely  quartan.  The  paroxysm  occurs 
more  often  during  the  night  than  in  the  case  with  the  adult, 
the  fever  being  often  detected  for  the  first  time  in  the  morning. 

The  first  stage  is  rarely  typic,  the  rigor  being  replaced  by 
coldness  of  the  extremities,  pallor,  slight  cyanosis,  especially  of 
the  lips,  and  nails,  vomiting,  drowsiness,  and  sometimes  con- 
vulsions. During  the  second  stage  the  fever  is  ordinarily  higher 
than  in  the  adult.  Gastro-intestinal  symptoms,  particularly 
vomiting  and  diarrhea,  are  common.     Thirst  is  usually  intense. 


138  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

The  most  common  complaints  are  pain  in  the  head  and  epigastric 
region.  Enlargement  of  the  spleen  is  more  constant  than  in  the 
adult.  Torticollis  and  erythema  may  be  noted.  Atypical 
forms  and  dangerous  symptoms,  especially  on  the  part  of  the 
nervous  and  gastro-intestinal  systems,  are  frequent.  Edema, 
ascites,  and  purpura  are  not  uncommon. 

Malaria  in  the  Negro. — The  relative  immunity  of  the  negro 
race  to  the  severe  manifestations  of  malaria  and  to  hemoglob- 
inuric  fever  has  been  mentioned.  It  remains  only  to  cite  a  few 
clinic  features  of  malaria  in  this  race. 

Estivo-autumnal  malaria  is  much  more  common  in  the  colored 
race  than  are  tertian  and  quartan.  The  paroxysms  usually 
occur  during  the  day,  but  night  paroxysms  are  more  common 
than  in  the  white  race.  A  well-defined  and  severe  cold  stage, 
while  not  at  all  rare  in  the  negro,  is  more  frequently  lacking 
than  in  the  accesses  in  the  white.  Herpes  is  relatively  rarer  in 
the  black.  Uncontrollable  vomiting  is  not  nearly  so  frequent 
in  the  colored  race  as  in  the  white.  Marked  splenic  enlarge- 
ment is  much  less  common  in  the  negro,  palpable  spleens  in  the 
adult  negro  being  infrequent.  The  extremely  low  hemoglobin 
percentages,  which  are  not  rare  in  chronic  malaria  and  cachexia 
of  white  persons,  are  far  less  frequently  observed  in  the  negro. 
As  previously  stated,  cachexia  is  decidedly  more  prevalent  in 
the  white  race.  Malaria  parasites  are  altogether  absent  from 
the  peripheral  blood  of  negroes  in  a  larger  per  cent,  of  cases  than 
they  are  wanting  in  white  patients.  When  present  they  are 
more  frequently  scanty.  On  the  other  hand,  the  negro  may 
harbor  large  numbers  of  parasites  without  manifesting  any 
symptoms.  Pulmonary  complications,  bronchitis,  pneumonia, 
and  tuberculosis  are  more  frequent  in  the  negro.  Nephritis  is 
another  complication  of  which  this  is  true.  Hysteria  and  other 
neuroses  are  probably  more  common  in  the  colored  female. 
The  abuse  of  snuff,  which  is  undermining  the  nervous  stability 
of  the  majority  of  adult  negro  females  in  the  South,  may  help  to 
account  for  this.  There  is  less  tendency,  to  abort  during  preg- 
nancy complicated  with  malaria  in  the  colored  females  than  in 
the  white.  Spontaneous  cure  after  only  one  or  two  paroxysms 
is    a   common   termination  of  malaria  in  the  negro.     Every 


MALARIA  139 

physician  practising  among  this  race  is  familiar  with  the  fre- 
quency with  which  their  attacks  of  malaria  end  after  a  "round" 
of  purgative  and  a  potion  of  "tea"  of  some  sort.  The  grave 
forms  of  malaria  occurring  less  often,  the  mortality  is  conse- 
quently lower  in  the  negro  race. 

The  Surgical  Aspect  of  Malaria. — Trauma  may  aggravate 
active  malaria  or  arouse  it  from  latency.  On  the  other  hand, 
malarial  infection  reacts  upon  wounds.  Slight  wounds,  such 
as  that  caused  by  the  extraction  of  a  tooth,  may  in  cachectics 
give  rise  to  excessive  hemorrhage.  Fractures  heal  more  slowly 
in  malarial  subjects.  I  have  more  than  once  observed  suppura- 
tion, ulceration,  and  sloughing  in  the  wounds,  aseptically  treated, 
of  malarial  persons,  especially  sawmill  employees  and  timber- 
men.  If  surgical  measures  are  contemplated  in  patients  with  a 
history  of  recent  malaria  the  blood  should  be  examined  care- 
fully for  evidences  of  malaria,  which,  if  present,  might  figure 
in  the  result. 


CHAPTER  V 
DIAGNOSIS  OF  MALARIA 

There  are  three  sources  from  which  information  may  be 
drawn  to  make  a  diagnosis  of  malaria:  first,  from  the  symptoms; 
second,  from  the  examination  of  the  blood;  and  third,  from  the 
effect  of  quinine  upon  the  symptoms. 

I.  Of  the  clinic  history  the  most  important  feature  to  be 
considered  is  periodicity.  Tertian  and  quartan  periodicity  are 
pathognomonic  of  malaria.  Sometimes  the  statements  of 
patients  cannot  be  relied  on  with  respect  to  the  course  of  their 
ailments,  and  tertian  and  quartan  periodicity  must  be  abso- 
lutely determined  to  be  of  diagnostic  value.  By  this  is  not 
meant  that  the  disease  must  be  observed  by  the  physician  un- 
treated until  such  periodicity  is  established,  but  that  value  of 
this  symptom  is  in  proportion  to  the  reliability  of  the  source 
from  which  the  history  is  derived.  .  Unfortunately,  this  peri- 
odicity is  of  little  value  in  estivo-autumnal  infections,  in  which 
the  importance  and  difficulty  of  diagnosis  are  greater. 

Quotidian  periodicity  is  not  only  worthless,  but  actually  mis- 
leading in  the  diagnosis  of  malaria.  It  is  especially  in  septic 
conditions  that  mistakes  are  oftenest  made,  where  not  infre- 
quently is  the  rhythmic  quotidian  succession  of  chill,  fever,  and 
sweat  mistaken  for  the  metric  march  of  malaria.  A  noted 
clinician  has  said  that  he  has  rarely  seen  a  case  of  abscess  of  the 
liver  that  had  not  been  drenched  with  quinine,  and  his  experience 
is  not  unique  in  this  respect.  Malaria  is  by  no  means  the  only 
condition  accompanied  with  cold,  hot  and  sweating  stages,  and 
one  or  two  of  these  stages  are  sometimes  wanting  in  malaria. 
Abscess  of  the  liver,  gall-stone  disease,  tuberculosis,  and  numer- 
ous other  diseases  may  exhibit  temperature  charts  closely  re- 
sembling that  of  malaria. 

It  should  be  borne  in  mind,  however,  that  quotidian  fever  in 
malaria  may  show  tertian  or  quartan  periodicity.     Thus  in 


MALARIA  141 

double  tertian  the  paroxysms  of  the  first  and  third  days  may 
occur  at  a  certain  hour  in  the  morning,  and  those  of  the  second 
and  fourth  days  at  a  certain  hour  in  the  afternoon.  Tertian 
periodicity  in  quotidian  fever  is  valuable  from  a  diagnostic  view 
in  proportion  as  the  paroxysms  on  successive  days  are  separated 
from  a  given  hour,  or,  in  other  words,  as  the  alternate  paroxysms 
approach  a  forty-eight-hour  interval,  while  the  accesses  on 
successive  days  are  distant,  by  more  or  less,  from  a  twenty-four- 
hour  interval.  Quartan  periodicity  in  quotidian  fever  rarely 
comes  into  consideration  in  diagnosis  on  account  of  the  relative 
rarity  of  the  triple  quartan  infections,  the  promptness  with 
which  the  microscope  decides  the  matter,  and  the  more  fre- 
quent tendency  of  one  or  two  of  the  three  groups  of  parasites 
to.  sporulate  approximately  twenty-four  hours  after  the  last 
preceding.  The  course  of  a  double  quartan  infection,  two 
successive  fever  days  followed  by  a  fever-free  day,  is  pathog- 
nomonic. 

It  may  be  stated,  as  a  general  rule,  that  tertian  and  quartan 
periodicity  are  of  importance  in  diagnosis  in  proportion  to 
the  length  of  the  series  of  paroxysms,  since  it  is  not  impossible 
that  fever  on  only  two  days  separated  by  one  or  two  days 
of  apyrexia  might  occur  adventitiously  from  causes  other 
than  malaria.  It  is  the  repetition  of  this  succession  that 
indicates  malaria;  hence  the  periodicity  must  be  perfectly 
established. 

The  characteristic  curve  of  tertian  estivo-autumnal  fever  is 
probably  pathognomonic,  but  can  be  obtained  in  only  a  small 
proportion  of  cases  in  private  practice.  The  clinical  course  of 
estivo-autumnal  infections  is  of  much  less  value  in  diagnosis 
than  that  of  tertian  and  quartan. 

The  value  of  enlargement  of  the  spleen  in  the  diagnosis  of 
malaria  has  certainly  been  over-rated.  In  regions  where  there 
is  little  malaria,  the  endemic  index  being  low,  it  is  probably  a 
point  of  some  worth.  On  the  other  hand,  in  malarial  regions 
of  high  index  endemicus  it  is  worth  much  less.  It  is  almost 
valueless  in  malaria  occurring  in  negroes,  as  it  is  infrequently 
sufficiently  enlarged  to  be  palpable,  and  unless  palpable  is  of 
no  diagnostic  value.     Physicians  in  malarial  regions  are  all 


142  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

familiar  with  the  frequency  with  which  the  enlarged  spleen  of 
the  subject  of  chronic  malaria  or  cachexia  complicates  other 
diseases.  If  the  physician  is  sufficiently  familiar  with  the  pa- 
tient to  know  that  the  splenic  enlargement  is  acute,  it  becomes 
a  matter  of  some  importance,  but  the  statement  of  the  patient 
as  to  the  former  condition  of  the  organ,  even  when  the  latter  is 
immense,  is  not  always  to  be  reUed  upon. 

Herpes  when  present  is  an  aid  to  diagnosis.  The  only  dis- 
ease in  which  it  occurs  with  anything  like  the  frequency  it 
does  in  malaria  is  pneumonia. 

2.  The  microscopic  examination  of  the  blood  for  the  diagnosis 
of  malaria  determines  the  presence  or  absence  of  parasites, 
pigment,  and  leucocytosis,  and  the  numeric  relation  of  the 
leucocytes. 

Before  attempting  the  diagnosis  of  malaria  by  the  micro- 
scopic examination  of  the  blood  the  beginner  must  become  thor- 
oughly familiar  with  the  appearance  of  normal  blood  and  with 
the  technic  of  examination,  and  he  should  not  rely  too  much 
upon  the  result  of  an  examination  until  he  has  had  consider- 
able experience  with  malarial  blood. 

While  Laveran  made  his  discovery  with  a  one-sixth-inch  lens, 
only  a  one-twelfth-inch  oil  immersion  lens,  with  appropriate 
condenser  and  diaphragm,  should  be  employed,  and  the  mechanic 
stage  greatly  facihtates  the  work.  Thin  slides  and  cover- 
glasses  should  be  used. 

While  stained  films  of  the  blood  have  a  wider  field  of  useful- 
ness to  the  general  practitioner  than  preparations  of  the 
unstained  blood,  he  should  become  familiar  with  the  technic 
of  each. 

When  about  to  obtain  blood  to  be  examined,  fresh  and  un- 
stained, several  slides  and  cover-glasses,  having  been  washed 
thoroughly  with  soap  and  water,  then  with  alcohol,  should  be 
rubbed  thoroughly  with  an  old,  clean  handkerchief  and  gently 
warmed.  While  the  blood  may  be  obtained  elsewhere,  the 
lobe  of  the  ear  has  advantages  over  other  locations:  it  is  less 
sensitive,  it  being  possible  to  obtain  blood  from  sleeping  children 
without  awakening  them;  the  instrument  and  the  blood  may  be 
kept  from  the  view  of  the  patient,  an  advantage  when  deaHng 


143 


Fig.  39. — Obtaining  the  blood  between  slide  and  cover-glass. 


144  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

with  children  and  nervous  persons.  More  blood  is  easily  ob- 
tained if  desired  to  make  a  hemoglobin  estimation,  blood  count, 
or  Widal  test.  The  lobe  of  the  ear  should  be  cleaned  with 
soap  and  water,  then  with  alcohol,  and  should  be  dried  thor- 
oughly. It  is  then  grasped  between  the  thumb  and  forefinger, 
the  latter  uppermost.  The  puncture  is  made  preferably  with 
a  large  straight  Hagedorn  needle  and  should  be  made  quickly 
to  the  depth  of  about  one-eighth  inch.  The  first  one  or  two 
drops  should  be  wiped  away  and  one  chosen  which  is  not  too 
large. 

The  cover-glass,  held  by  diagonal  corners  between  the  thumb 
and  forefinger  or,  better,  by  means  of  forceps,  is  applied  to  the 
summit  of  the  blood-drop  and  laid  face  down  upon  the  slide. 
Care  must  be  taken  to  touch  only  the  top  of  the  drop  and  not 
the  skin,  otherwise  the  blood  smeared  upon  the  cover-glass  will 
have  begun  to  coagulate  around  the  margin  and  will  not  spread 
freely.  It  is  a  common  mistake  to  take  too  large  a  drop  of 
blood,  and  if  the  blood  extends  to  the  edges  of  the  cover-glass 
and  the  center  of  the  film  has  a  ground-glass  appearance  it 
should  be  discarded.  If  the  blood  does  not  spread  freely  and 
evenly  it  is  better  not  to  use  pressure,  but  the  cover-glass  may 
be  gently  pushed  by  the  needle  appHed  to  its  edge.  Several 
preparations  should  be  made  to  insure  a  good  one,  and  each  time 
the  ear  should  be  wiped  free  of  blood  and  a  fresh  drop  taken. 
A  rim  of  vasehne  around  the  edges  of  the  cover-glass  will  pre- 
serve the  specimen  longer. 

As  simple  as  this  seems,  it  requires  considerable  practice  to 
obtain  films  in  which  the  red  cells  lie  side  by  side  and  not  in 
rouleaux. 

Hayem's  method  gives  better  results  in  the  hands  of  the 
amateur.  A  square  cover-glass  is  placed  upon  a  sKde  in  such  a 
manner  that  one  edge  of  the  cover-glass  coincides  exactly  with 
the  edge  of  the  slide  near  its  middle.  Held  rather  firmly  in 
this  position  by  the  thumb  and  forefinger,  the  coapted  edges  are 
applied  to  the  blood-drop,  when  the  blood  spreads  evenly  be- 
tween the  slide  and  cover-glass.  When  the  blood  has  almost 
reached  the  opposite  edge  of  the  cover-glass,  enough  blood  has 
been  obtained.     Two  cover-glasses  may  be  used  instead  of  a 


145 


Fig.  42. — The  cigarette-paper  method. 


146  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

slide  and  cover-glass,  and  when  ready  to  be  examined  one  of  the 
cover-glasses  cemented  at  the  corner  or  edge  to  a  slide  by  means 
of  Canada  balsam. 

The  advantages  of  dried  films  over  fresh  preparations  of 
blood  are  several.  Cleanliness  of  the  part  from  which  the  blood 
is  taken  and  the  size  of  the  drop  are  not  so  important.  This 
advantage  is  appreciated  by  the  practitioner  who  often  has  to 
make  the  preparation  in  the  remote  corner  of  an  ill-lighted 
cabin.  The  slides  may  be  laid  aside  and  examined  at  leisure, 
weeks  or  even  months  later.  The  differential  leucocyte  count 
can  be  made  on  the  same  shde. 

It  is  not  necessary  that  the  region  from  which  the  blood  is 
taken  should  be  perfectly  clean,  but  if  prespiration  is  present 
this  should  be  wiped  off.  The  ear  is  held  and  the  puncture 
made  as  described  for  wet  films.  The  sHde  held  in  the  right 
hand,  is  rested  against  the  thumb  and  forefinger  holding  the 
lobe  of  the  ear,  and  gradually  lowered  until  it  receives  the  drop 
of  blood  near  one  end. 

The  smear  may  be  made  by  either  one  of  three  useful  methods. 
The  simplest  is  to  hold  the  slide  in  the  left  hand  and  with  the 
right  lay  the  shaft  of  the  needle  across  the  drop  of  blood.  After 
waiting  a  few  moments  for  the  blood  to  spread  out  between 
the  needle  and  the  shde,  the  needle  is  evenly  and  gradually 
drawn  to  the  opposite  end  of  the  slide.  Drying  the  film 
by  rapidly  waving  it  in  the  air  preserves  the  form  of  the  red 
cells. 

Instead  of  the  needle  the  end  of  another  slide  may  be  applied 
to  the  drop  of  blood  so  that  the  two  slides  meet  at  an  angle  of 
about  45  degrees;  after  waiting  for  the  blood  to  spread  along  the 
edge  of  the  slide,  the  upper  slide  is  then  drawn  to  the  opposite 
end  of  the  lower,  and  the  film  dried  by  waving. 

Cigarette  paper  may  be  used  as  follows:  Strips  about  three- 
fourths  of  an  inch  wide  are  cut  perpendicularly  to  the  ribs  of 
the  paper;  the  end  of  one  of  these  strips,  the  original  machine- 
cut  edge,  is  applied  to  the  blood-drop  near  the  end  of  the  slide, 
and  after  a  few  moments  drawn  to  the  opposite  end  of  the  slide. 
Other  paper  may  be  employed  if  cigarette  paper  is  not  available, 
but  does  not  answer  so  well. 


MALARIA  147 

If  flies  gain  access  to  unstained  films,  they  will  rapidly  devour 
the  blood. 


Fig.  43. — Making  films  upon  cover-glasses. 

Many  staining  methods  have  been  proposed  to  demonstrate 
the  malarial  parasite  in  the  blood.     A  common  mistake  for  the 


Fig.  44. — If  the  forceps  are  applied  to  the  center  of  the  slide  the  stain  will 
not  run  off. 


student  to  make  is  to  attribute  bad  results  to  the  stain,  and  to 
discard  a  method  before  he  has  become  familiar  with  it.     In 


148  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

no  branch  of  pathology  is  attention  to  minute  details  of  technic 
of  greater  influence  upon  results,  and  a  method  should  be  thor- 
oughly mastered  before  passing  judgment  upon  it. 

Malaria  parasites  take  basic  stains,  of  which  methylene  blue 
is  most  frequently  employed. 

Wright's  stain  gives  beautiful  results  but  does  not  keep  well 
after  being  mixed.  It  has  the  advantage  also  of  being  one  of 
the  quickest  stains. 

I  am  now  using  the  following  method.  The  films  are  fixed 
in  absolute  methyl  alcohol  for  about  half  a  minute.  After 
drying,  this  stain  is  freshly  mixed  and  poured  on;  allow  it  to 
remain  ten  or  fifteen  minutes: 

Watery  eosin  in  water,  i :  500 5  drops 

Azure  II  in  water,  i :  500 5  drops 

Distilled  water 30  drops 

Wash  in  distilled  water,  dry  with  filter  paper,  place  cedar  oil 
directly  on  the  film  and  examine. 

The  examination  should  be  protracted  for  thirty  minutes  be- 
fore being  pronounced  negative.  While  parasites,  if  present, 
are  usually  found  within  five  or  ten  minutes,  it  is  not  uncommon 
to  detect  the  first  organisms  after  a  search  of  twenty  to  thirty 
minutes. 

Cedar  oil  may  be  removed  from  the  film  by  wiping  gently 
with  a  soft  cloth  moistened  with  xylol. 

The  "thick  film  process"  is  occasionally  useful  where  the 
parasites  are  very  scanty.  The  blood  is  smeared  upon  the  slide 
in  a  much  thicker  layer  than  for  other  methods.  After  drying, 
a  little  distilled  water  is  added  and  allowed  to  remain  fifteen 
minutes,  which  causes  the  dissolution  of  the  hemoglobin.  After 
drying  again  the  film  is  stained  by  one  of  the  usual  methods. 
While  the  outline  of  the  red  cells  are  still  visible,  the  cells  are 
transparent  and  parasites  may  be  detected,  though  lying  under 
several  cells.  The  advantage  of  this  method  is  that  a  much 
larger  volume  of  blood  may  be  examined  in  a  shorter  space  of 
time  than  is  the  case  with  the  thin  film.  The  method  described 
by  Henson^^''  is  valuable  also. 

Flagella  are  much  more  easily  demonstrated  in  the  gametes  of 


MALARIA  149 

the  estivo-autumnal  than  of  the  tertian  and  quartan  parasites. 
The  crescent  becomes  oval  and  then  spheric  before  exflagella- 
tion  is  observed.  To  encourage  this  process  a  number  of  rather 
thick  drops  of  blood  are  placed  upon  a  series  of  slides.  The 
slides  are  then  inverted,  with  the  hanging  drops  over  holes  cut 
in  blotting  paper,  moistened  with  water,  and  spread  on  a  pane 
of  glass.  A  series  of  moist  chambers  is  thus  made.  A  slide  is 
removed  at  intervals  of  five  minutes,  the  blood  spread  in  the 
usual  manner  and  stained.  Exflagellation  is  also  observed  in 
preparations  of  fresh  blood.  The  warm  stage,  breathing  upon 
the  specimen,  and  the  addition  of  a  little  water  are  recommended 
to  hasten  the  process. 

Sources  of  Error. — In  the  examination  of  blood  for  malarial 
parasites  there  are  several  objects  which  may  mislead.  Pitfalls 
are  probably  more  common  in  fresh  blood  than  in  stained  films. 
Vacuoles  and  retractions  of  hemoglobin  in  red  cells  of  fresh 
preparations  are  delusive  and  not  infrequently  mistaken  for  the 
young  hyaline  forms  of  the  parasite.  They  are  most  common  in 
the  center  of  the  cell,  while  parasites  are  found  in  any  portion. 
Vacuoles  are  highly  refractive,  having  well-defined,  clear-cut 
edges;  the  margins  of  the  parasites  are  dim  and  fade  gradually 
into  the  substance  of  the  red  cells.  The  vacuoles  may  show 
slight  changes  of  form,  but  do  not  possess  true  ameboid  motion 
nor  pigment.  While  the  vacuoles  are  perfectly  clear,  the  para- 
sites show  a  slight  opalescence.  In  stained  specimens  areas 
which  do  not  take  the  stain  may  deceive.  These  areas  may  be 
of  circular  form  in  the  center  of  the  cell,  or  of  ring  form  surround- 
ing the  center,  or  may  be  oval,  horseshoe-shaped,  crucial  or 
irregular.  When  present  they  are  apt  to  be  abundant  in  some 
portions  of  the  film  and  entirely  absent  elsewhere. 

Crenation  of  red  cells  may  present  a  hyaline  appearance  some- 
what resembling  an  ameboid  parasite.  Their  nature  may  be 
determined  by  changing  the  focus. 

Bent  or  buckled  corpuscles  occasionally  resemble  crescents. 
The  absence  of  pigment  and  the  size  of  the  corpuscle  should, 
however,  enable  a  distinction.  Overlapping  of  the  corpuscles 
produce  a  ring  or  crescent  appearance  which  deceives  the 
beginner. 


150  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

The  object  in  stained  spreads  which  proves  most  deceiving  to 
the  inexperienced  is  probably  the  blood  platelet.  These  cor- 
puscles may  lie  upon  or  within  the  red  cells,  in  the  center,  near 
the  periphery,  or  only  partially  enclosed  by  them.  They  are 
from  one-seventh  to  one-half  the  size  of  a  red  blood-cell,  and  are 
round,  oval,  or  elongated  in  shape.  They  are  often  of  mul- 
berry shape  and  reticular  structure,  and,  with  the  Romanowsky 
class  of  stains,  approach  more  nearly  purple  or  lilac  than  the 
characteristic  blue  of  the  parasites.  The  margin  is  surrounded 
by  a  pale  or  unstained  area  resembling  a  halo.  There  is,  of 
course,  an  absence  of  pigment  and  chromatine.  Occurring  in 
groups,  as  it  frequently  does,  it  has  not  rarely  been  mistaken 
for  a  sporulating  body  and  isolated  for  a  free  spore.  Bodies 
resembling  free  spores  should,  however,  be  disregarded  for  diag- 
nostic purposes. 

The  nuclei  of  nucleated  red  corpuscles  may  be  mistaken  for 
parasites,  but  this  should  rarely  occur  if  the  morphology  and 
staining  reactions  of  both  bodies  are  borne  in  mind. 

Pigmented  leucocytes  have  been  mistaken  for  parasites, 
but  the  ameboid  motion  of  the  former  in  fresh  specimens 
and  the  staining  reactions  in  dried  films  should  prevent 
confusion. 

Hemokonia,  or  blood-dust,  may  be  confused  with  free  spores. 
They  are  small,  highly  refractive,  micrococcus-like  bodies 
averaging  one-half  micron  in  diameter  and  possessed  of 
very  animated  motion.  As  stated,  free  spores  should  not  be 
sought  for  diagnosis,  and  bodies  resembling  them  should  be 
ignored. 

Extraneous  dirt,  leucocyte  granulations,  and  stain  precipi- 
tates must  be  carefully  distinguished  from  pigment. 

The  amateur  in  examinations  of  malarial  blood  is  apt  to  be- 
come decidedly  discouraged,  even  when  he  has  satisfactorily 
mastered  the  technic  in  the  laboratory.  Most  students  gain 
the  impression  that  all  that  is  necessary  to  find  the  parasites  is 
to  locate  a  malarial  subject  with  any  form  of  the  disease  and 
obtain  the  necessary  blood  at  any  stage  of  parasitic  develop- 
ment, to  stain  it  properly,  and  to  inspect  it  under  a  high-power 
lens.     Usually    this    is    what   he   has   been    taught   by   text- 


MALARIA  151 

books  and  by  teachers,  and  when  he  fails  to  detect  the  char- 
acteristic organisms  in  undoubted  cases  of  malaria  he  is  dis- 
gusted. The  results  of  such  teaching  throw  discredit  upon  a 
discovery  whose  practical  importance  is  unsurpassed  in  modern 
medicine. 

To  estimate  the  value  of  a  report  on  the  result  of  microscopic 
examination  of  the  blood  for  malarial  parasites  it  is  always 
desirable  to  know  something  of  the  experience  of  the  examiner. 
In  addition  to  competence  and  proper  technic  there  are  several 
factors  which  influence  the  result  of  the  examination  for  para- 
sites. The  most  important  of  these  are:  (a)  the  previous  ad- 
ministration of  quinine;  (b)  the  stage  of  development  of  the 
organisms;  (c)  the  stage  of  the  disease;  (d)  the  type  of  infection; 
(e)  race;  (/)  locality;  and  (g)  individual  circumstances. 

(a)  The  previous  administration  of  quinine,  even  in  small 
quantities,  renders  it  almost  useless  to  examine  the  blood  with 
the  expectation  of  finding  parasites.  Even  where  the  quantity 
of  the  drug  is  insufficient  to  have  any  effect  on  the  symptoms, 
it  will  ordinarily  cause  a  disappearance  of  the  parasites  from 
the  peripheral  circulation.  The  half-poisoned  parasites  which 
persist  in  some  instances  are  frequently  unrecognizable  with 
reference  to  type. 

(b)  The  quartan  parasite  is  nearly  evenly  distributed  in  all 
its  phases,  from  the  youngest  form  to  the  sporulating  body, 
throughout  the  superficial  and  deep  circulation.  Hence,  when 
dealing  with  this  type  it  makes  little  difference  at  what  period 
the  blood  is  examined.  But  with  the  estivo-autumnal  organ- 
ism it  is  only  the  early  stages,  the  small  rings,  that  are  observed 
with  any  degree  of  frequency  in  the  peripheral  blood,  and  if  the 
examination  is  made  when  the  parasite  has  reached  a  later 
stage  of  development  it  will  probably  be  missed.  Instead  of 
resembling  the  quartan  parasite  in  habit  of  distribution  it  seems 
to  imitate  its  more  distant  relative,  the  Leishman-Donovan 
parasite.  Later  phases  of  the  simple  tertian  hematozoon  are 
less  commonly  found  in  examinations  of  the  peripheral  blood 
than  those  of  the  quartan,  but  are  much  more  frequently  ob- 
served than  those  of  the  estivo-autumnal.  Sporulating  bodies , 
of  the  quartan  type  are  not  uncommon  in  the  cutaneous  blood, 


152  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

while  those  of  the  tertian  are  much  less  common  and  those  of 
the  estivo-autumnal  extremely  uncommon. 

The  frequency  with  which  crescents  are  detected  varies  within 
the  broadest  confines.  In  the  experience  of  some  they  are  rare, 
while  other  observers  note  them  frequently  in  estivo-autumnal 
infections.  Tertian  gametes  are  not  rarely  observed  in  the 
blood  of  the  superficial  circulation,  while  quartan  gametes  are 
scarcely  found. 

(c)  In  acute  untreated  malaria  the  parasite  can  be  detected 
at  some  stage  of  its  growth  in  almost  100  per  cent,  of  cases. 
If  not  found  at  the  first  examination,  as  frequently  occurs, 
subsequent  searches  are  usually  successful.  On  the  contrary, 
in  chronic  malaria  the  parasites  are  far  from  constant  during 
the  stage  of  latency,  and  prolonged  search  may  fail  to  reveal 
them  during  the  relapse.  Parasites  are  often  absent  from  the 
peripheral  blood  of  malarial  cachectics.  In  the  paramalarial 
syndrome,  hemoglobinuric  fever,  the  parasites,  if  present  before 
onset,  afterward  disappear  in  the  majority  of  cases. 

(d)  The  behavior  of  the  dift'erent  kinds  of  parasites  in  their 
various  stages  has  been  referred  to.  As  a  rule,  the  quartan 
parasite  is  most  certainly  found  on  first  examination,  the  estivo- 
autumnal  least  so,  on  account  of  its  habit  of  resorting  to  the 
deep  circulation  when  approaching  maturity.  It  is  very  un- 
fortunate for  rapid  diagnosis  that  the  estivo-autumnal  parasites 
are  less  readily  detected  than  those  of  the  benign  infections, 
but,  fortunately,  are  usually  found  easily  in  pernicious  cases  of 
estivo-autumnal  infection. 

(e)  That  malaria  parasites  are  found  less  frequently  and  in 
smaller  numbers  in  the  superficial  circulation  of  negroes  with 
malaria  I  am  convinced,  though  the  difference  is  slight. 

(/)  Along  the  northern  borders  of  malarial  distribution  the 
parasites  are  probably  more  readily  detected.  This  may  be 
accounted  for  partially  by  the  greater  relative  frequency  of 
simple  tertian  infections.  Whether  the  more  northern  negro 
shows  the  same  scanty  distribution  of  parasites  in  the  peripheral 
blood  as  manifested  by  his  southern  brother  I  have  no  means 
of  determining.  It  is  surprising  with  what  frequency  crescents 
are  found  in  higher  latitudes  in  the  blood  of  patients  moving 


MALARIA  153 

from  highly  malarial  localities  where  crescents  are  not  so  fre- 
quently observed.  Whether  this  is  a  conservative  measure 
related  to  the  relative  rarity  of  anopheline  mosquitoes  cannot 
be  stated  positively,  but  it  is  known  that  the  life  histories  of 
animals  are,  in  some  instances,  peculiarly  interdependent, 
especially  in  the  case  of  parasite  and  host. 

(g)  Why  it  is  that  in  certain  unquestionable  cases  of  malaria 
which  have  received  no  quinine  and  in  which  every  condition 
seems  favorable  to  finding  the  parasites  prolonged  and  repeated 
examination  shows  none  is  not  known,  but  such  cases  are  some- 
times encountered. 

As  before  said,  where  the  specilic  can  be  withheld  and  re- 
peated examinations  made  by  a  competent  microscopist  if 
not  found  at  the  first  examination,  the  parasite  may  be  found 
in  almost  100  per  cent,  of  cases  of  malaria.  The  question, 
which  is  of  the  utmost  practical  importance  to  the  physician, 
arises:  In  what  proportion  of  cases  is  the  parasite  to  be  found 
at  a  single  examination?  On  this  depends  in  great  measure 
the  practical  value  of  Laveran's  discovery,  for  in  not  a  few  cases 
in  general  practice  for  reasons  of  convenience  the  examination 
cannot  be  repeated;  in  others  in  which  the  diagnosis  seems  more 
or  less  clear  urgent  symptoms  are  demanding  the  specific. 
The  two  factors  which,  more  than  the  others,  influence  the  result 
are  whether  or  not  the  patient  has  received  quinine  and  the 
phase  of  parasitic  development  attained  when  the  blood  is 
withdrawn  for  the  examination.  Neither  of  these  factors  is 
always  within  the  control  of  the  physician  who  desires  to  make 
a  diagnosis  upon  examination  of  the  blood  taken  when  the  pa- 
tient first  comes  under  his  observation.  Since  a  very  large 
proportion  of  the  malaria  of  the  land  is  treated  by  country 
doctors,  the  practical  value  of  a  diagnostic  test  is  largely  in 
proportion  as  it  is  applicable  by  them. 

With  reference  to  the  number  of  cases  in  which  the  parasite 
can  be  found  at  the  first  examination  I  will  state  my  experience. 
From  a  record  kept  of  the  number  of  malarial  cases  which  had 
taken  quinine  in  some  form  before  coming  under  observation 
it  was  learned  that  this  reached  something  over  50  per  cent. 
of  the  total  number  of  cases  treated.     The  diagnosis  in  these 


154  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

cases  was  obviously  based  upon  the  clinical  history  and  the  thera- 
peutic test,  since  the  search  for  parasites  in  the  blood  of  persons 
having  received  quinine  is  so  discouraging  that  this  has  not 
been  done  in  routine  work,  but  only  in  special  cases.  Allowing 
for  errors  in  diagnosis  might  reduce  this  number  to  50  per  cent. 
A  specimen  of  blood  was  always  taken  from  malarial  patients 
who  had  not  recently  received  quinine  when  they  came  under  ob- 
servation for  the  first  time,  irrespective  of  the  stage  of  the  access. 
The  blood  from  frank  cases  only  has  been  included,  no  cases 
of  atypic  or  latent  malaria  or  of  cachexia  figuring  in  the  result. 
Parasites  were  found  in  approximately  two-thirds  of  the  cases 
and  the  examination  was  negative  in  about  one-third.  No 
difference  as  to  clinical  course,  severity,  or  the  efiicacy  of  quinine 
could  be  detected  between  the  cases  in  which  parasites  were 
found  and  those  in  which  none  were  observed.  From  this  ex- 
perience it  may  be  inferred  that  In  localities  in  which  half  of 
the  malarial  subjects  take  quinine  in  some  form  before  con- 
sulting a  physician  the  parasite  can  be  detected  at  a  single 
examination  of  the  peripheral  blood,  taken  at  random  with 
respect  to  the  stage  of  parasitic  growth,  in  approximately  one- 
third  of  the  cases  only.  The  prevalence  of  self-medication  with 
quinine  products  depends  largely  upon  local  custom  and  upon 
the  energy  of  the  patent-medicine  industry. 

My  experience  being  somewhat  at  variance  with  the  con- 
ventional text-book  teaching,  I  feel  it  incumbent  to  cite  the 
experience  of  others  in  this  matter  of  the  most  vital  interest. 

Craig*^^  says,  "Often  if  the  blood  be  examined  but  once  none 
at  all  will  be  found." 

Fornario^i^  observes  that  the  parasites  are  missed  with  ex- 
treme frequency,  and  Soliani,"'^"  in  an  analysis  of  61 2  cases  under 
his  care,  says  that  in  many  cases  the  first  examination  was 
negative. 

McElroy^^^  says,  "  I  have  been  struck  with  the  frequency  with 
which  I  have  been  unable  to  find  parasites  in  cases  where  I  am 
strongly  impressed  with  the  malarial  nature  from  the  clinical 
history." 

Plehn^-^  states  that  the  parasites  are  frequently  lacking  in  the 
malaria  of  natives,  or  at  least  they  are  not  found  in  the  peripheral 


MALARIA  155 

blood,  where  the  temperature  curve  is  typic  and  pigmented 
leucocytes  indicated  malaria. 

The  experience  of  Ewing''^  at  Camp  Wikoff  is  interesting. 
"In  the  605  cases  of  malaria  the  plasmodia  were  found  in  the 
blood  of  335  cases,  while  in  270  cases  the  diagnosis  was  based 
upon  the  clinical  history  and  the  discovery  in  the  blood  of 
evidences  of  malarial  infection.  The  evidences  of  malarial  in- 
fection in  the  blood  consisted  (i)  usually  in  the  presence  of  intra- 
cellular bodies  so  much  affected  by  quinine  that  their  exact  type 
could  not  be  positively  determined;  or  (2)  in  the  presence  of 
typic  pigmented  leucocytes;  or  (3)  in  chronic  cases  of  distinct 
cHnical  character  in  the  presence  of  marked  anemia." 

Leonard  Rogers,'^  than  whom  there  is  no  more  competent 
observer,  says:  "As  long  ago  as  1896  I  showed  from  an  exami- 
nation of  100  cases  of  consecutive  malarial  fever  before  the 
adnrdnistration  of  quinine  that  in  only  one-third  of  them  could 
the  malarial  parasite  be  found  by  means  of  a  prolonged  search 
of  a  single  blood  film." 

Delaney's^--  experience  is  even  more  disheartening.  He  con- 
cludes: "I  think  that  I  shall  be  supported  by  most  competent 
observers  in  India  that  this  (17  per  cent.)  about  represents  the 
percentage  of  success  in  finding  malarial  parasites  in  the  malarial 
fevers  of  India  at  a  single  examination,  and  on  this  point  both 
text-books  and  writers  on  the  subject  are,  I  consider,  very  mis- 
leading." 

Such  quotations  from  practical  workers  and  deep  observers 
could  be  multiplied,  but  could  add  no  further  weight  to  the 
authority  of  those  cited. 

The  above  statements  are  not  meant  to  cast  the  slightest 
doubt  upon  the  etiologic  role  of  the  parasite  of  malaria,  or  its 
presence  in  every  case  of  acute  untreated  malaria,  or  its  great 
diagnostic  value  under  certain  circumstances,  but  are  intended 
to  demonstrate  that  the  detection  of  the  parasite  is  subject  to 
several  conditions.  In  probably  no  other  disease,  associated 
with  a  pathognomonic  sign  which  can  be  ehcited  in  almost  100 
per  cent,  of  cases,  is  its  detection  so  dependent  upon  conditions 
beyond  the  control  of  the  physician. 

What  is  the  value  of  a  positive  result  of  examination  of  the 


156  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

blood  for  malarial  organisms?  This  parasite  is  thoroughly 
established  as  the  sole  cause  of  malaria,  and  its  pathogenic 
reputation  has  never'  been  marred  by  rumors  of  etiologic  asso- 
ciation with  other  diseases.  But  is  the  parasite,  when  present, 
responsible  for  the  symptoms  which  instigate  the  blood  ex- 
amination? 

In  localities  where  a  considerable  per  cent,  of  the  inhabitants 
carry  malaria  germs  in  their  blood  without  showing  malarial 
symptoms  it  is  manifestly  possible  that  parasites  might  be 
found  in  the  blood  of  such  inhabitants  during  the  course  of  other 
ailments.  And  such  is  actually  the  case  in  certain  regions  with 
a  very  high  endemic  index,  to  such  an  extent,  indeed,  that  the 
widely  experienced  Albert  Plehn,^^  in  Cameroon,  declared  that 
the  presence  or  absence  of  malarial  parasites  in  the  blood  of  the 
West  African  coast  negro  is  of  no  diagnostic  value. 

In  cases  of  coma  in  which  malarial  parasites  are  detected  and 
which  give  a  history  of  exposure  to  violent  heat  or  of  the  abuse 
of  alcohol,  it  is  not  infrequently  difhcult  to  determine  the  part 
played  by  the  parasite.  In  cases  of  coma  accompanied  by 
malarial  parasites  in  the  blood  and  albumin  and  casts  in  the 
urine  the  diagnosis  may  be  obscure.  Fever  occurring  during 
the  puerperium  in  subjects  of  former  malaria  will  make  the 
thoughtful  physician  uneasy  for  a  short  while  at  least,  even  if 
parasites  are  found  on  blood  examination. 

These  are  mainly  problems,  however,  which  are  involved  in 
other  fields  of  diagnosis  and  serve  to  impress  the  fact  that  com- 
plications must  be  excluded  or,  if  found,  weighed.  While 
these  contingencies  should  not  be  lost  sight  of,  in  the  immense 
majority  of  cases  in  tliis  country  active  forms  of  the  malarial 
parasite  detected  in  the  blood  are  responsible  for  the  symptoms 
which  bring  the  patient  under  the  care  of  the  physician  or  which 
prompt  the  physician  to  make  the  examination. 

It  will  be  noted  that  the  word  active  is  emphasized.  What, 
then,  is  the  value  to  be  attached  to  the  discovery  of  gametes 
alone? 

Formerly  it  was  believed  that  the  sole  function  of  these 
peculiar  bodies  was  the  perpetuation  of  the  species  through  the 
mosquito  cycle.     Under  this  Hmited  view  the  detection  of  gam- 


MALARIA  157 

etes  alone  was  on  a  diagnostic  par  with  anemia  and  splenome- 
galy, sequelae  of  malaria,  and  not  necessarily  proof  of  existing 
malaria,  even  latent.  Since  it  has  become  known  however, 
that  under  certain  not  well  understood  conditions  the  macro- 
gametes  can  immediately,  by  the  process  of  parthenogenesis, 
give  rise  to  pyrogenic  parasites  without  undergoing  the  mos- 
quito cycle,  our  views  must  be  modified,  and  these  forms  must 
be  regarded  chnically  as  the  parasites  of  latent  malaria.  Rela- 
tive to  active  malaria,  they  may  be  looked  upon  as  evidences  of 
past  and  potential,  but  not  necessarily  of  present,  active  malaria. 

What  is  the  diagnostic  value  of  a  negative  result? 

I  can  by  no  means  agree  with  those  who  maintain  that  such  a 
result  positively  excludes  a  diagnosis  of  malaria.  The  failure 
to  find  parasites  in  the  blood  of  a  single  film  taken  without 
reference  to  the  period  of  the  paroxysm,  while  of  some  value,  is 
not  conclusive,  and  if  the  patient  has  recently  received  quinine 
is  absolutely  worthless.  On  the  other  hand,  if  the  blood  of  a 
patient  who  has  not  recently  taken  quinine  be  examined  repeat- 
edly by  a  competent  person  with  the  result  that  no  parasites 
are  found,  it  is  very  strong  evidence  against  malaria.  The  diag- 
nostic value,  then,  of  a  negative  finding  depends  upon  the  pres- 
ence or  absence  of  the  conditions  which  have  been  enumerated, 
the  chief  of  which  is  the  administration  of  quinine. 

When  the  examination  of  the  peripheral  blood  is  negative, 
puncture  of  the  spleen  has  been  advised,  as  the  parasites  in  all 
stages  are  easily  detected  in  the  blood  of  this  organ.  This 
procedure,  however,  is  attended  with  some  degree  of  danger, 
especially  of  hemorrhage,  and  should  be  resorted  to  only  in 
cases  where  an  immediate  diagnosis  is  imperative.  It  has  been 
estimated  that  the  mortality  of  aspiration  of  the  spleen  is 
iH  per  cent.*^ 

Upon  failure  to  discover  parasites  in  the  blood  there  are  two 
other  blood  signs  which  must  be  considered.  These  are  the 
presence  of  pigment  and  a  relative  increase  in  the  large 
mononuclear  leucocytes.  These  signs  are  termed  subsidiary 
evidences  of  malaria,  because,  being  secondary  in  diagnostic 
importance  to  the  parasites,  they  are  generally  called  upon 
only  in  the  absence  of  the  latter. 


158  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Melanin  is  pathognomonic  of  malaria,  and  its  presence  is 
not  contingent  upon  the  stage  of  development  of  the  parasites 
or  upon  the  previous  administration  of  quinine.  Theoretically, 
therefore,  it  should  be  of  the  greatest  significance  in  the  diag- 
nosis of  malaria.  There  are,  however,  certain  circumstances 
which  detract  from  its  practical  value.  Free  pigment,  or  that 
lying  upon  red  blood-cells,  should  be  ignored  in  the  diagnosis,  as 
it  cannot  be  distinguished  from  adventitious  detritus.  Within 
the  large  mononuclear  leucocytes,  the  leucocytes  in  which 
it  is  most  frequently  found,  it  must  be  carefully  distinguished 
from  the  minute  pigment-like  granulations  which  may  occur 
normally  in  these  cells  to  the  number  of  one,  two,  or  three  to 
each  cell.  This  requires  a  considerable  degree  of  experience. 
Coarse  granules  of  pigment  are  much  more  readily  recognized, 
especially  in  fresh  blood.  In  stained  films  precipitates  may 
prove  very  confusing.  Pigment  may  persist  for  two  or  three 
days  after  the  last  paroxysm  in  tertian  and  quartan  infections, 
and  for  a  much  longer  period  in  estivo-autumnal.  It  is  more 
valuable  as  a  diagnostic  sign  of  chronic  malaria  than  of  acute. 

The  second  subsidiary  sign  of  malaria,  a  relative  increase  of 
the  large  mononuclear  leucocytes,  is  under  some  conditions  a 
valuable  aid  to  a  diagnosis.  The  proportion  of  large  mono- 
nuclear elements  in  the  differential  count  is  modified  by  certain 
factors  which  detract  somewhat  from  its  value. 

In  early  childhood  there  is  normally  an  increase  of  mono- 
nuclear leucocytes;  hence  this  sign  need  not  be  sought  for  in 
the  malaria  of  young  children. 

As  with  other  diagnostic  evidences  of  malaria,  this  sign  is 
unfortunately  more  constant  and  more  marked  in  tertian  and 
quartan  infections  than  in  estivo-autumnal. 

The  increase  of  the  large  mononuclear  leucocytes  in  malaria 
is  generally  in  inverse  proportion  to  the  height  of  the  tempera- 
ture, being  most  decided  in  the  interval,  and  may  be  absent 
during  pyrexia.  An  increase  may  be  wanting  also  early  in  first 
attacks. 

When  there  is  evidence  of  leucocytosis  the  differential  count 
alone  must  not  be  relied  upon,  since  an  absolute  increase  may 
exist  under  these  circumstances  when  the  differential  count 


MALARIA  159 

will  show  only  a  small  per  cent.  Here  the  absolute  count  must 
be  made  also. 

In  differentiating  malaria  from  typhoid  fever  the  differential 
count  is  of  value  only  in  the  first  two  weeks  of  a  fever,  since 
after  that  time  the  relative  proportions  of  the  leucocytes  are 
similar  in  the  two  diseases. 

Notwithstanding  its  difficulties,  the  differential  leucocyte 
count,  made  by  an  experienced  examiner,  may  render  important 
aid  in  the  diagnosis  of  malaria  where  the  parasite  cannot  be 
detected,  and  a  mononuclear  leucocytosis  reaching  15  per  cent, 
must  be  regarded  as  strong  evidence  of  malaria. 

Besides  the  presence  of  pigment  and  a  large  mononuclear 
increase  there  is  another  point  ascertained  by  microscopic  ex- 
amination of  the  blood;  this  is  the  presence  or  absence  of  leuco- 
cytosis. Between  malaria  and  typhoid  fever  this  point  has  no 
differential  value,  and  it  will  be  remembered  that  a  leucocytosis 
is  frequent  in  pernicious  malaria.  It  is,  however,  in  septic 
conditions  which  sometimes  so  closely  resemble  malaria  in  which 
a  marked  leucocytosis  may  serve  to  exclude  malaria. 

The  Therapeutic  Test. — Here  diagnosis  and  treatment  meet 
very  closely,  the  former  encroaching  somewhat  upon  the  field 
of  the  latter,  the  diagnostic  test  often  becoming  a  therapeutic 
and  life-saving  measure.  The  therapeutic  test  is  of  especial 
value  in  cases  which  have  already  had  insufficient  quinine, 
thereby  causing  only  the  disappearance  of  the  parasites  from 
the  superficial  circulation  and  distortion  of  the  fever  curve. 
In  these  cases  it  has  at  least  as  much  standing  in  clinical  medi- 
cine as  antisyphilitics  in  obscure  cases  thought  to  be  syphilis 
or  antitoxin  in  cases  of  suspicious  angina  in  which  a  bacteriologic 
examination  is  impossible.  When  properly  applied  it  can 
hardly  be  productive  of  harm. 

A  fever  which  resists  quinine  is  not  a  malarial  fever.  In 
order  to  test  the  resistance  of  fever  to  quinine  the  drug  must  be 
continued  for  a  sufficient  length  of  time  and  in  proper  doses 
at  suitable  intervals,  and,  what  is  most  important,  it  must  be 
absorbed. 

The  maximum  period  of  resistance  of  malaria  to  quinine  is 
ordinarily  stated  as  four  days.     As  far  as  my  observations  go, 


l6o  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

they  tend  to  show  that  in  many  cases  the  fever  is  broken  by 
the  end  of  thirty-six  hours,  in  at  least  half  of  the  cases  in  forty- 
eight  hours,  and  in  three-fourths  the  cases  in  sixty  hours.  It 
is  highly  probable  that  in  cases  of  malaria  persisting  longer 
than  four  days  the  specific  is  not  being  absorbed.  A  case  is 
recalled  in  which  the  fever  continued  notwithstanding  the  ad- 
ministration in  capsules  of  24  grains  of  a  soluble  salt  of  quinine 
during  the  twenty-four  hours  for  nearly  six  days.  Parasites 
having  been  found  before  the  quinine  was  begun,  the  drug  was 
then  given  in  solution,  when  the  fever  responded  during  the 
seventh  day.  There  had  been  no  evidences  of  cinchonism 
until  the  solution  was  employed.  Cinchonism,  however,  is  not 
a  guide  in  the  employment  of  the  therapeutic  test;  the  specific 
is  directed  toward  the  parasites  and  not  toward  the  patient,  and 
patients  manifest  various  degrees  of  sensitiveness  toward 
quinine. 

Owing  to  the  conditions  under  which  the  therapeutic  test 
is  usually  employed  it  is  better  to  use  moderate  doses  at  reg- 
ular intervals  during  both  day  and  night.  Three  or  four  grains 
every  three  hours  are  sufficient.  Pills  and  tablets  of  quinine 
should  never  be  relied  upon;  the  result  may  be  not  only  mis- 
leading but  dangerous.  Capsules,  if  fresh,  are  usually  satis- 
factory; a  few  pin  punctures  in  each  end  aids  solution.  Where 
the  fever  persists  and  there  is  reason  to  believe  that  the  medicine 
is  not  being  absorbed  it  should  be  given  in  solution  or  even  intra- 
muscularly. 

The  period  of  apyrexia  following  a  single  dose  of  quinine  corre- 
sponds closely  to  the  parthenogenetic  cycle.  The  conquest  of 
the  schizonts  seems  to  be  a  signal  for  the  macrogametes  to  lay 
aside  the  conventionahty  of  slow  sexual  reproduction  and  to 
conscript  recruits  rapidly  by  parthenogenesis. 

Not  every  fever  which  discontinues  after  the  administration 
of  quinine  can  be  considered  malarial,  since  such  an  occurrence 
is  occasionally  coincidental.  Furthermore,  it  is  well  known  that 
quinine  has  no  little  antipyretic  influence  upon  certain  condi- 
tions, particularly  septic. 

It  is  probably  superfluous  to  say  that  the  diagnosis  of  malaria 
does  not  always  consist  alone  in  the  mere  mechanic  application 


MALARIA  l6l 

of  a  single  test,  but  that  in  some  cases  the  keenest  chnic  judg- 
ment is  required.  Of  the  several  diagnostic  signs  which  we 
possess  each  is  valuable  and  each  has  its  limitations. 

It  should  be  a  routine  practice  to  take  a  specimen  of  blood 
from  each  fever  patient. 

In  dealing  with  a  disease  in  which  the  blood  examination 
affords  pathognomonic  evidence  and  for  which  we  possess  a 
specific  the  dilemma  is  often  faced,  where  the  examination  of 
the  first  specimen  of  blood  is  negative,  of  having  to  decide 
whether  it  is  best  to  wait  a  few  hours  for  an  absolutely  certain 
diagnosis  or  to  take  advantage  of  every  hour  and  begin  the 
treatment  immediately.  If  quinine  has  already  been  taken  the 
chances  are  that  further  examinations  would  also  be  negative, 
and  the  better  course  would  be  to  proceed  with  the  specific. 
If  quinine  has  not  already  been  taken  and  the  symptoms  are  not 
urgent  the  case  may  be  treated  symptomatically  for  a  little 
while,  during  which  time  the  blood  is  examined  at  appropriate 
intervals. 

In  hospital  practice  the  practical  value  of  the  blood  examina- 
tion for  malaria  parasites  is  inestimable;  in  general  practice, 
especially  in  the  rural  districts,  its  value  is  more  limited.  In 
general  practice,  especially  in  the  country,  the  therapeutic  test 
is  of  great  value;  in  hospital  practice  it  is  less  often  justifiable. 

DIFFERENTIAL  DIAGNOSIS 

Abscess  of  the  Liver. — Septic  conditions  are  very  often  diag- 
nosed as  malaria;  this  is  especially  true  of  hepatic  abscess. 
There  are  two  classes  of  cases  of  abscess  of  the  liver  that  may  be 
difiicult  at  first  examination  to  distinguish  from  malaria: 
first,  where  the  local  symptoms  are  absent  or  not  well  defined; 
second,  where  there  is  enlargement  of  both  liver  and  spleen  and 
a  history  of  both  dysentery  and  malaria.  The  fact  that  these 
patients  have  usually  been  drenched  unsystematically  with 
quinine  may  compHcate  the  diagnosis.  In  typic  cases  of  hep- 
atic abscess  there  is  usually  a  history  of  dysentery,  and  amebae 
may  be  present  in  the  feces.  There  is  usually  a  dragging  pain 
in  the  Hver,  sometimes  referred  to  the  right  shoulder,  increase 


l62  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

of  liver  dulness,  and  tenderness  on  pressure.  The  spleen  is  not 
necessarily  enlarged.  The  temperature  does  not  often  rise 
high  and  there  is  apt  to  be  profuse  perspiration,  especially  dur- 
ing sleep.  On  microscopic  examination  of  the  blood  there  is 
usually  a  leucocytosis  to  be  found,  though  this  is  wanting  in  a 
few  cases,  and  its  absence  should  not  be  taken  to  exclude  abscess. 
There  are  neither  parasites,  pigment,  nor  a  relative  increase  of 
the  large  mononuclear  leucocytes.  Exploratory  aspiration  is 
valuable  in  some  cases.  Jaundice  is  a  very  variable  symptom 
and  may  be  misleading. 

Infective  endocarditis  may  present  periodic  paroxysms  of 
chill,  fever,  and  sweat.  The  physical  examination  of  the  heart 
and  the  microscopic  examination  of  the  blood  should  establish 
the  diagnosis. 

Puerperal  Septicemia. — Women  who  have  had  malaria  dur- 
ing pregnancy  are  prone  to  suffer  relapses  during  the  puerperium. 
In  this  condition  malaria  is  not  infrequently  atypic;  the  first  or 
third  stages  of  the  paroxysm  are  sometimes  lacking  and  com- 
plete intermission  of  temperature  is  often  wanting.  The  fol- 
lowing may  serve  to  differentiate  typic  cases  of  malaria  and  puer- 
peral sepsis: 

Malaria  Puerperal  Septicemia 

Onset  from  a  few  hours  to  twenty-one  Rare  after  the  fifth  day. 

days  after  labor. 

Often  a  history  of  malaria.  Malarial  history  usually  absent. 

Temperature  curve  more  or  less  typic.  Irregular. 

Symptoms  decline  with  temperature.  No   relation    between   symptoms  and 

temperature. 

No  local  symptoms.  Local  symptoms  present. 

Blood  examination  positive.  Negative. 

Therapeutic  test  positive.  Negative. 

The  so-called  urethral  fever  may  be  accompanied  by  parox- 
ysms somewhat  resembhng  those  of  malaria.  I  have  recently 
seen  a  case  in  which  the  introduction  of  a  steel  sound  every 
other  day  was  accompanied  for  a  short  time  by  corresponding 
paroxysms  not  due  to  malaria.  The  differentiation  from  ma- 
laria should  present  no  difi&culties. 

Perinephric  abscess,  pyelitis,  cholecystitis,  and  other  septic 
processes  may  be  associated  with  fever  which  bears  a  more  or 


MALARIA  163 

less  close  resemblance  to  that  of  malaria.  Local  symptoms,  the 
blood  examination,  and  the  therapeutic  test  rarely  leave  the 
diagnosis  in  doubt  but  a  short  while. 

In  proportion  to  the  rehance  placed  upon  symptomatology 
in  the  differentiation  of  tjrphoid  and  malarial  fevers  so  frequently 
will  mistakes  occur.  Chills,  continued  fever,  bronchitis,  en- 
larged spleen,  slight  tenderness  and  gurgling  in  the  right  iliac 
fossa,  tympanites,  diarrhea,  the  Diazo  reaction,  deUrium,  and 
the  typhoid  state  may  occur  with  either  disease.  Herpes  is 
strongly  indicative  of  malaria  and  rose  spots  of  typhoid  fever, 
but  these  spots  are  more  frequently  absent  than  present  in  the 
typhoid  fever  of  warm  countries. 

A  correct  diagnosis  must  rest  upon  the  results  of  the  examina- 
tion of  the  blood  and  the  therapeutic  test. 

Tuberculosis  is  sometimes  similar  in  its  course  to  malaria. 
It  is  especially  so  in  the  early  stage  when  the  local  signs  and 
symptoms  are  ill  defined  or  absent  and  the  bacillus  cannot  be 
detected,  and  in  the  stage  of  secondary  infection  when  septic 
symptoms  supervene.  Miliary  tuberculosis  has  not  infre- 
quently been  mistaken  for  malaria.  For  the  diagnosis  between 
tuberculosis  and  malaria  the  microscopic  examination  of  the 
blood  and  sputum,  the  physical  examination  and  therapeutic 
test  are  usually  ample. 

Influenza  has  sometimes  been  confused  with  malaria.  If  the 
epidemic  occurrence,  different  seasonal  prevalence,  catarrhal 
and  other  symptoms  are  insufficient  upon  which  to  make  a 
diagnosis,  the  absence  of  characteristic  blood  findings  is  gen- 
erally conclusive. 

Yellow  fever  in  some  cases  so  closely  resembles  the  so-called 
bilious  remittent  fever  that  in  regions  where  both  diseases 
occur  the  differential  diagnosis  by  clinical  history  alone  is 
impossible.  In  such  instances  the  microscope  becomes  an  in- 
strument of  the  greatest  good  not  only  to  the  individual,  but  to 
the  community. 

The  frequency  with  which  dysentery  is  associated  with  malaria 
as  a  complication  and  as  a  sequel  renders  the  microscopic 
examination  of  the  blood  very  important  in  these  cases. 

Patients  with  syphilis  manifesting  quotidian  fever  not  infre- 


164  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

quently  receive  quinine  instead  of  antisyphilitics.  The  micro- 
scope, the  therapeutic  test,  the  Wassermann  reaction,  and  the 
history  should  form  the  basis  of  the  diagnosis. 

Before  the  geographic  distribution  of  the  hook-worm  and  its 
importance  in  the  production  of  anemia  became  recognized, 
uncinariasis  was  not  distinguished  from  chronic  malaria  and 
cachexia.  The  detection  of  the  ova  in  the  feces,  the  presence 
of  eosinophilia,  the  absence  of  parasites  and  the  subsidiary 
evidences  of  malaria  in  the  blood  render  such  a  mistake  at  the 
present  time  inexcusable. 

Leukemia  must  occasionally  be  taken  into  consideration  in 
the  differential  diagnosis  of  malaria,  in  which  case  the  micro- 
scopic examination  of  the  blood  is  absolutely  essential. 

The  differentiation  of  Banti's  disease  from  chronic  malaria  and 
cachexia  may  be  extremely  difficult.  We  will  not  solve  the 
mysteries  of  splenomegaly  until  we  learn  a  safe  method  of  ob- 
taining blood  from  the  spleen. 

THE  DIAGNOSIS  OF  PERNICIOUS  MALARIA 

In  the  immense  majority  of  cases  examination  of  the  per- 
ipheral blood  will  reveal  the  presence  of  the  organisms.  The 
value  of  this  is  inestimable  and  is  paralleled  only  by  the  im- 
portance of  making  blood  examinations  in  all  cases.  It  is  not 
extremely  uncommon  in  our  cities  for  subjects  of  pernicious 
attacks  found  in  coma  to  be  taken  to  the  police  station  instead 
of  the  hospital  and  the  true  condition  not  suspected  until  the 
patients  fail  to  "sober  up"  in  due  time,  when  it  is  usually  too 
late  for  treatment  to  avail. 

In  cases  showing  the  presence  of  parasites,  complications 
must  be  rigidly  excluded.  In  some  cases  this  is  attended  with 
difi&culties. 

In  comatose  malaria,  besides  the  evidence  obtained  by  an 
examination  of  the  blood,  a  history  of  exposure  to  or  attacks  of 
malaria,  the  general  appearance  and  age  of  the  patient,  the 
absence  of  atheroma,  the  early  elevation  of  temperature,  and 
perhaps  the  enlargement  of  the  spleen  and  slight  jaundice 
should  exclude  cerebral  hemorrhage.     The  differentiation  of 


MALARIA  165 

malarial  coma  from  sunstroke  is  often  hard;  in  fact,  the  two  not 
infrequently  coexist,  in  which  case  it  may  be  impossible  to 
apportion  the  etiologic  share  of  each  in  the  clinical  picture. 
Cardamatis'"^  states  that  in  this  type  of  pernicious  malaria 
coma  is  the  dominating  symptom,  while  in  sunstroke  are  ob- 
served coma,  convulsions,  delirium,  and  hyperpyrexia.  Uremic 
coma  may  simulate  that  due  to  malaria.  Unfortunately,  the 
urinalysis  throws  no  light  on  the  diagnosis,  as  in  both  conditions 
we  may  find  albumin  and  casts.  The  blood  examination,  the 
temperature,  and  the  anamnesis  serve  to  make  the  diagnosis. 
For  the  differentiation  of  alcoholic  from  malarial  coma  the  blood 
examination  is  essential.  The  history  may  be  of  value,  but  the 
odor  of  the  breath  may  be  misleading.  To  discriminate  be- 
tween malarial  coma  and  diabetic  coma  the  presence  of  the 
parasites,  on  one  hand,  and  of  glycosuria,  on  the  other,  are  suf- 
ficient. In  differentiating  between  the  various  comas  with 
reference  to  malaria  two  points  should  be  remembered:  First, 
that  comatose  malaria  may  occur  in  persons  with  the  odor  of 
alcohol  on  the  breath,  and,  secondly,  that  coma  from  causes 
other  than  malaria  may  attack  malarial  cachectics.  To 
distinguish  epilepsy,  opium  poisoning,  tetanus,  and  meningitis 
from  pernicious  malaria  should  rarely  present  difficulties  if  the 
blood  is  examined. 

Algid  attacks  sometimes  resemble  perforation  of  typhoid,  or 
gastric  ulcers,  or  rupture  of  the  spleen.  The  microscope  and 
the  local  symptoms  should  render  the  diagnosis  certain.  The 
cases  resembling  appendicitis  and  peritonitis  have  been  men- 
tioned; here,  again,  the  microscopic  examination  of  the  blood 
may  save  lives.  In  countries  in  which  cholera  is  endemic,  the 
diagnosis  between  this  disease  and  the  choleraic  type  of  pernicious 
malaria  was  formerly  difficult  or  impossible.  Laveran's  dis- 
covery has  removed  this  difficulty  and  rendered  possible  a 
diagnosis  of  the  utmost  importance.  The  finding  of  the 
hematozoa  differentiates  the  hemorrhagic,  bilious,  and  typhoid 
types  from  typhoid  and  yellow  fevers. 


CHAPTER  VI 
PROGNOSIS  OF  MALARIA 

Spontaneous  Recovery. — While  physicians  in  malarial  re- 
gions often  see  patients  whose  paroxysms,  typic  and  with  char- 
acteristic periodicity,  have  ceased  without  medication  or  after 
nothing  but  a  purgative  dose,  it  is  doubtful  whether  this 
cessation  may  with  propriety  be  termed  a  cure.  In  the  major- 
ity of  instances  relapses  follow  at  shorter  or  longer  intervals. 
It  is  better,  therefore,  for  practical  purposes  to  consider  this 
but  a  transition  from  active  malaria  to  latency.  The  greater 
frequency  with  which  gametes  are  found  after  the  so-called 
spontaneous  recovery  justifies  this  assumption. 

Spontaneous  cure  occurs  more  frequently  in  tertian  and  quar- 
tan infections.  This  statement  applies  merely  to  the  temporary 
cessation  of  paroxysms  and  not  to  the  tendency  to  relapse. 

It  is  more  frequently  observed  in  the  negro  than  in  the  white 
race,  permanent  cures  occurring  not  rarely  in  the  former  race 
in  the  absence  of  all  medication. 

Sex  may  exert  a  slight  influence  upon  the  tendency  to  spon- 
taneous recovery,  the  female,  on  account  of  less  severe  ex- 
posure to  deleterious  influences,  probably  manifesting  a  greater 
disposition. 

The  discontinuance  of  paroxysms  may  be  sudden  or  more 
often  gradual,  the  accesses  becoming  less  severe  or  the  interval 
longer,  or  in  infections  with  more  than  one  generation  of  para- 
sites one  may  be  suddenly  destroyed,  the  others  later. 

Prognosis. — This  is  influenced  to  some  extent  by  locality. 
It  is  manifest  that  in  regions  where  only  the  tertian  and  quartan 
infections  are  prevalent  the  mortality  is  less  than  where  severe 
estivo-autumnal  fevers  are  widespread.  There  is,  furthermore, 
quite  a  difference  in  the  mortality  rate  in  countries  where  the 
estivo-autumnal  infections  are  equally  distributed. 

Race  as  a  factor  in  the  mortality  of  malaria  has  already 
been  dealt  with. 

i66 


MALARIA  167 

A  majority  of  deaths  from  malaria  occur  in  children.  There 
is  no  doubt  but  that  many  children  die  of  malaria  which  has 
not  been  diagnosed  in  time.  In  the  young,  pernicious  symp- 
toms, especially  cerebral,  are  prone  to  supervene,  or  the  attack 
may  be  followed  by  extreme  anemia  and  dropsies.  Malaria 
is  likewise  much  more  serious  in  advanced  age  than  in  the  inter- 
mediate ages. 

Occupation  and  social  conditions  play  a  part  in  prognosis. 
Excessive  toil  and  exposure  may  render  pernicious  attacks 
otherwise  benign,  and  timely  treatment,  usually  resorted  to  by 
the  better  classes,  enhances  the  chance  of  recovery. 

The  outlook  is  probably  more  favorable  in  attacks  occurring 
without  the  malarial  season  than  within. 

Manifestly  the  condition  of  the  patient  with  reference  to  the 
results  of  previous  disease  is  of  importance.  Anemia,  alcohol- 
ism, dysentery,  and  other  conditions  not  fully  recovered  from, 
contribute  gravity  to  the  prospect. 

The  t)^e  of  malarial  infection  is  of  the  greatest  importance. 
In  the  tertian  and  quartan  types  it  is  only  very  rarely  that 
serious  symptoms  result.  It  is  not  yet  certainly  known  in 
which  variety  of  estivo-autumnal  infection  the  prognosis  is 
most  grave. 

Postponement  and  anticipation  of  the  paroxysms  were  form- 
erly regarded  as  favorable  and  unfavorable,  respectively. 
However,  owing  to  the  irregularity  of  the  estivo-autumnal  fevers, 
these  can  be  said  strictly  to  be  properties  of  tertian  and  quartan 
infections  only,  and  are  consequently  of  little  prognostic  import. 
Violent  headache,  somnolence,  sighing  respiration,  slight  mental 
aberration,  defective  articulation  and  vision,  cold  surface,  and 
rapid,  feeble  pulse  are  some  of  the  symptoms  which  forebode  evil. 

The  prognostic  value  of  the  microscopic  examination  of  the 
blood  is  limited.  While,  as  a  general  rule,  the  severity  of  the 
attack  is  in  proportion  to  the  number  of  parasites,  these  are 
sometimes  scanty  in  the  peripheral  circulation  even  in  grave 
cases.  Sporulating  and  advanced  stages  of  estivo-autumnal 
parasites  are  rarely  seen  in  the  superficial  blood  except  in  ex- 
tremely severe  cases. 

While  in  tertian  and  quartan  infections  a  paroxysm  may  be 


1 68  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

predicted  approximately  from  the  results  of  blood  examination, 
such  an  attempt  with  estivo-autumnal  malaria  may  prove  mis- 
leading. An  impending  paroxysm  dependent  on  mature  para- 
sites in  the  visceral  circulation  cannot  be  foretold. 

Intercurrent  diseases  complicating  malaria  aggravate  the 
prognosis.  This  is  especially  the  case  in  chronic  malaria  and 
cachexia,  with  which  pneumonia,  dysentery,  and  other  dis- 
eases form  frequently  fatal  associations. 

The  gravity  of  pregnancy  as  a  complication  of  malaria  has 
been  considered. 

In  nephritis  of  malarial  origin  the  prospect  is,  as  a  rule,  good. 
If,  however,  the  patient  is  repeatedly  subjected  to  malaria  or 
other  harmful  influences  the  prognosis  is  not  propitious. 

The  prognosis  of  the  nervous  sequelae  is  ordinarily  favorable. 
The  various  paralyses  and  mental  symptoms  are  generally 
transitory,  but  may  occasionally  become  persistent.  Bulbar 
symptoms  are  usually  slow  to  disappear. 

The  course  of  chronic  cachexia  may  be  extended  for  years; 
acute  cachexia  runs  a  more  rapid  course.  In  mild  cases  a  change 
of  climate  and  tonic  treatment  do  a  great  deal  for  the  patient; 
advanced  cases  rarely  recover.  Death  may  occur  from  ex- 
haustion, but  is  more  commonly  due  to  pernicious  malaria  and 
to  complications,  of  which  the  most  frequent  are  pneumonia  and 
nephritis.  Hence  the  danger  to  the  cachectic  is  not  confined 
to  the  malarial  season,  but  he  is  in  danger  throughout  the  entire 
year. 

Mortality. — The  true  mortahty  of  malaria  is  difficult  to  esti- 
mate. While  statistics  are  not  lacking,  the  different  conditions 
under  which  they  are  complied  must  be  considered,  some  being 
from  charity  hospitals,  some  from  private  practice,  some  from 
military  practice,  from  various  localities,  etc.  It  is,  further- 
more, undoubtedly  true  that  a  considerable  proportion  of  mala- 
rial cases  does  not  come  to  the  notice  of  physicians.  The 
variety  of  forms  which  malaria  assumes  is  another  obstacle. 
It  is  probable  that  many  cases  ascribed  to  complications,  fancied 
or  real,  are  due  to  malaria. 

Bearing  these  points  in  mind,  the  following  figures  are  pre- 
sented, showing  a  mortality  of  2.89  per  cent. : 


169 


Laveram-' 

Laveran^' 

Laveran^^ 

Schellong"" 

Ross*-'' 

Ross"^ 

Ewing'^ 

Smart"^" 

Travers'''" 

Terburgh-"" , 

Cardamatis'" 

Koch"^ 

Koch" 

Hagen'-' 

British  Colonial  Reports*^*. 

Wright"^ 

Haw"« 

Hope"" 

Laveran*'" 

Gorgas''" 

Erni'" 

United  States  Marine  Hos- 
pital532 

Various  Hospital  Reports. . 

German  Protectorate  Re- 
ports*''  

Malaria  Society"' 


Locality 

Turko-Russian  War   . 

Constantine 

Italian  Army 

New  Guinea 

Greece 

Hong  Kong 

Camp  Wikoff 

Civil  War 

Malay  States 

Dutch  Indies 

Athens 

Grosseto 

East  Africa 

Papua 

British  Colonies 

British  Malaya 

Baberton 

North  Bengal 

Algiers 

Panama 

Dutch  Indies 

General 

Southern  States 

German  Protectorates 
Italy 


140,000 

1,092 

1,31° 

0 

4,856 

13 

1,954 

22 

960,048 

5,916 

7,352 

984 

60s 

39 

1,373,355 

15.423 

3,397 

348 

2,308,128 

114,490 

22,618 

15 

281 

0 

63 

2 

301 

23 

12,617 

618 

17,648 

680 

449 

14 

1,784 

0 

98,774 

7,432 

1,055 

5 

116,879 

731 

6,618 

20 

1,294 

30 

5,003 

32 

22,792 

120 

5,109,001 

148,055 

Prognosis  of  Pernicious  Malaria. — The  prognosis  of  perni- 
cious malaria  is  extremely  grave.  It  depends  upon  the  physical 
condition  and  age  of  the  patient,  the  t3^e  and  severity  of  the 
attack,  and  the  promptness  and  efSciency  of  the  treatment. 
Anemia  from  previous  attacks  of  malaria  or  other  cases,  alco- 
holism, or  organic  disease  of  important  viscera,  add  to  the 
gravity  of  the  case.  The  cerebral  types  are  less  serious  in  the 
young  and  vigorous,  very  fatal  in  the  aged.  As  a  rule,  patients 
seen  early  and  treated  skilfully  and  energetically  have  a  better 
chance  for  life,  but  many  cases  end  fatally  in  spite  of  the  best 
and  most  timely  treatment. 

The  number  of  parasites  in  the  peripheral  circulation  is  not 


170 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


always  a  reliable  guide  as  to  the  severity  of  progress  of  the 
attack.  With  apparent  amelioration  of  the  symptoms  the 
physician  should  be  circumspect  in  his  prognosis  and  bear  in 
mind  the  possibility  of  further  paroxysms. 

In  my  opinion  the  algid  type  is  the  most  lethal,  the  typhoid 
and  the  dysenteric  least  so. 

The  following  list  of  27,039  cases  of  pernicious  malaria,  com- 
piled from  the  literature,  shows  a  mortality  of  26.6  per  cent. 
The  first  column  of  figures  shows  the  number  of  cases,  the  second 
the  number  of  fatalities: 


Xumber  of  deaths 


Laveran^^ 

Bailly"^ 

Nepple^' 

Antonini  and  Monard^^ 

Maillot^' 

Grall'^s 

Burot  and  Legrand'* 

Smart52<! 

Travers''''* 

Martirano*'^ 

Pezza*^^ 

Tanzarella''* 

Thayer  and  Hewetson'"' 

Plehn2 

Maillot"' 

Theophanidis*" 

Cardamatis^^' 

Pampoukis*^' 

Billett"s 

Segard'* 

MaureP" 

Caccini*-" 

Martirano'^" 

Charity  Hospital,  New  Orleans*'"' 

Near"' 

Celli"- 

Cardamatis''' 

Colonial  Reports*^' 

Kelsch  and  Kiener'* 

Albini"! 


S3 

341 

6 

9 


117 

75 

210 

142 

16,209 

4,164 

260 

81 

19 

9 

2 

I 

31 

8 

3 

2 

10 

I 

7 

6 

S 

2 

3 

2 

52 

20 

40 

2 

24 

15 

156 

77 

13s 

56 

6 

3 

8 

6 

3 

3 

8,032 

1,879 

5° 

9 

252 

133 

89 

51 

97 

ir 

MALARIA 


171 


Six  hundred  and  eighty-nine  cases  of  specified  type  give  the 
following  respective   mortalities: 


Comatose 

Delirious 

Algid 

Typhoid 

Ataxic 

Maillot^^ 

75-14 
7-6 

lO-I 

61-12 

48-12 

Schellon<''*'' 

Plehn' 

Maillot^'' 

7-6 
3-2 

Theophanldis^" 

Pampoukis'-' 

Billet"' 

52-20 

40-2 

Maurel*^' 

297-103 
3-3 

78-23 

22-17 

Neer^*' 

428-147 
34  per  cent. 

61-12 
20  per  cent. 

141-4S 
32  per  cent. 

40-2 
S  per  cent. 

22-17 
77  per  cent. 

CHAPTER  VII 
PROPHYLAXIS  OF  MALARIA 

Prophylactic  measures  may  be  directed  against  the  destruc- 
tion of  the  malaria  parasites  within  the  body  of  man,  the  de- 
struction of  the  mosquitoes  which  are  capable  of  transmitting 
the  parasites,  and  the  prevention  of  mosquitoes  gaining  access 
to  man.  The  parasite  may  be  opposed  either  in  man  or  in  the 
mosquito.  The  mosquito  may  be  combated  either  in  its 
aquatic  or  in  its  aerial  stage.  Prophylaxis  may  be  conducted 
by  a  community  or  by  an  individual,  may  be  public  or  private, 
offensive  or  defensive. 

As  is  well  known,  malaria  is  now  almost  or  entirely  absent 
from  regions  in  which  it  was  formerly  very  prevalent,  and  in 
other  places  is  rapidly  diminishing.  In  the  regions  in  mind  the 
change  was  independent  of  designed  efforts  for  the  eradication 
of  the  disease;  in  fact,  it  occurred  in  most  instances  before  the 
discovery  of  either  the  malaria  parasite  or  of  the  role  of  the  mos- 
quito in  the  dissemination  of  the  disease,  and  was  an  unexpected 
result  of  the  progress  of  civilization. 

With  the  tediously  attained  and  in  many  cases  incomplete 
results  of  this  unconscious  prophylaxis  are  in  decided  contrast 
the  consequences  of  well- organized  and  vigorous  sanitary  meas- 
ures directed  toward  the  prevention  of  malaria.  Many  in- 
stances could  be  adduced  where  within  a  comparatively  short 
space  of  time  highly  malarial  locaKties  have  been  almost  com- 
pletely freed  from  the  disease,  but  a  few  examples  will  suffice. 

One  of  the  most  successful  campaigns  against  malaria  was 
that  at  Ismailia,  a  town  of  about  8,000  inhabitants  near  the 
middle  point  of  the  Suez  Canal.  The  town  was  founded  in 
1862,  and  was  celebrated  for  its  salubrity  until  1877,  when 
malaria  was  introduced  and  spread  rapidly;  in  1886  nearly  all 
the  inhabitants  were  attacked.  In  1901  the  president  of  the 
Suez  Company,  learning  something  of  the  results  of  modern 
prophylactic  methods,  dispatched  Pressat,  a  member  of  the 


173 

■1. 


Fig.  45. — The  barrels  and  one  of  the  buckets  contained  many  larvae. 


Fig.  46. — Anopheles  larva;  in  the  barrel.     A  fatal  case  of  comatose  malaria 
occurred  here  a  few  weeks  before  the  picture  was  taken. 


174  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

medical  staff,  to  Italy  to  study  the  subject,  and  invited  Ross 
to  inspect  the  place  and  advise  upon  the  most  suitable  manner  of 
conducting  the  campaign.  In  September,  1902,  Ross  arrived 
in  company  with  MacGregor  and  with  Pressat  returning  from 
Italy.  An  abundance  of  anophelines  were  found  in  the  houses 
of  the  employees,  and  the  larvae  especially  in  small,  brackish 
marshes  in  the  sand  and  in  some  of  the  waters  of  irrigation,  but 
not  in  the  main  canal,  where  they  were  probably  destroyed  by 
fish.  It  was  evident  that  mosquito  reduction  was  to  be  the 
chief  end,  though  old  cases  of  malaria  received  vigorous  treat- 
ment.    Marshes  were  filled  with  sand  and  the  irrigation  channels 


were  deepened  or  treated  with  oil.  This  preliminary  work  was 
conducted  with  a  brigade  of  only  four  men,  though  many  others 
were  employed  later  for  the  extensive  permanent  work.  From 
1885  until  1902  inclusive  the  number  of  cases  of  malaria  at 
Ismailia  had  averaged  nearly  1,800  annually.  In  1903  there 
occurred  214  cases;  in  1904,  90;  and  in  1905  only  37.  It  is  said 
that  it  is  now  possible  to  sleep  with  comfort  in  the  place  without 
nets.  The  cost  of  the  campaign  is  estimated  at  an  initial 
expenditure  of  6.25  francs  and  an  annual  outlay  of  2.3  francs 
per  head  of  population. 

The  results  of  the  campaign  conducted  by  Travers  and  Wat- 
son at  Klang  and  Port  Swettenham,  in  the  Federated  Malay 
States,  are  hardly  less  striking.     Klang  had  3,576  inhabitants 


MALARIA 


175 


in  1 901.  Port  Swettenham,  five  miles  away,  had  a  population 
•of  about  700.  The  population  of  the  district  surrounding  the 
two  towns  was  about  14,000.     In  the  latter  part  of  1901  malaria 


Fire  barrels  containing  larvae. 


was  SO  extensively  prevalent  that  probably  not  more  than  three 
houses  in  Klang  escaped  infection,  and  Port  Swettenham  was 
being  abandoned  by  the  workmen.     The  antimalarial  campaign. 


Fig.  49. — Water  barrels  may  prevent  the  spread  of  fire,  but  will  breed  mosquitoes 
unless  covered. 

which  was  confined  to  the  towns  of  Klang  and  Port  Swettenham, 
began  in  1902.  Swamps  were  filled,  a  contour  drain  estabhshed 
to  intercept  incoming  water  from   surrounding  springs,   and 


176  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


.,  ,  '#■  %- 


Fig.  50. — Stock  pond  containing  anopheles  larvae.     Too  near  the  dwelling. 


Fig.   51. — A  protected  pool  in  a  lumber-yard  containing  myriads  of  anopheles 
larvie. 


MALARIA  177 

forest  and  mangrove  trees  were  felled.  After  the  epidemic 
had  begun  to  subside  screens  were  furnished  many  of  the  houses 
and  quinine  was  distributed.  The  cost  of  the  operations  to  the 
end  of  1905  consisted  of  a  primary  expense  of  £10,100  and  an 
annual  expense  of  £410. 

The  following  table  shows  the  mortality  from  malaria  within 
the  towns  as  compared  with  that  of  the  unprotected  district: 


1900 

1901 

1902 

1903 

1904 

190S 

Towns 

Districts 

....    2S9 

368 
266 

59 

2-7 

46 
230 

48 
286 

45 
351 

The  most  brilliant  results  in  the  prophylaxis  of  malaria  were 
those  obtained  by  Gorgas  in  Panama,  one  of  the  most  insalu- 
brious regions  upon  the  face  of  the  earth,  having  been  called 
during  French  occupation  "the  Frenchman's  grave."  It  is  a 
common  report  that  in  the  railroad  between  Panama  and  Colon 
every  cross-tie  represents  the  corpse  of  a  laborer. 

The  canal  zone  is  50  miles  in  length,  with  Panama  and  Colon 
at  each  end.  The  average  number  of  employees  is  40,000. 
The  efforts  consisted  in  the  destruction  of  breeding  places  only 
within  200  yards  of  the  camps  and  villages,  no  attempts  being 
made  to  deal  with  those  farther  off.  All  the  houses  were 
screened  and  the  people  were  urged  to  use  mosquito  bars. 
Quinine  was  furnished  them  and  they  were  advised  to  take  3 
grains  daily.  The  abolition  of  the  breeding  pools  was  regarded 
as  a  most  important  measure.  Owing  to  the  heavy  rainfall 
and  the  luxuriant  vegetation  the  ditches  filled  rapidly  with 
grass,  and  it  was  found  much  cheaper  to  concrete  them.  Sub- 
soiling  by  means  of  the  tile  drain  covered  with  rock  and  soil 
was  used  wherever  possible. 

The  result  is  that  the  death  rate  has  been  lowered  until  it 
does  not  exceed  that  of  New  York  City. 

I.  MEASURES  DIRECTED  FOR  THE  DESTRUCTION  OF 
MOSQUITOES 

Destruction  of  breeding  pools  for  the  anopheles  is  an  effi- 
cient preventive  measure.     It  is  chiefly  through  the  eradication 


lyS  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

of  breeding  places  that  so-called  unconscious  prophylaxis  has 
accompUshed  its  results.  This  method  has  received  the  chief 
consideration  in  the  greatest  antimalarial  campaigns.  It  is 
more  permanent  and  possesses  the  further  advantage  in  many 
instances  of  being  cheaper  in  the  end. 

It  is  neither  necessary  nor  in  every  case  advisable  to  remove 
the  surface  water  from  the  whole  of  a  malarial  country,  but 
only  in  the  regions  of  inhabitants  or  where  anopheles  are 
known  to  breed.  In  the  Panama  campaign  the  area  of  de- 
struction extended  only  200  yards  from  camps  and  habita- 


Fig.  52. — A  typical  "bayou,"  the  headquarters  of  malaria. 

tions.     This  should  probably  be  the  minimum  radius,  though 
work  at  a  much  greater  distance  is  only  a  useless  expense. 

In  the  area  to  be  protected  -the  land  should  be  cleared  of 
weeds,  undergrowth,  bushes,  and  unnecessary  trees  to  promote 
evaporation  and  prevent  the  formation  of  puddles.  Grocery 
cans,  broken  bottles,  buckets,  and  old  tinware  which  might 
retain  water  should  best  be  buried.  Water  barrels,  tanks, 
cisterns,  and  wells  should  be  emptied,  filled,  or  screened. 
Gutters  should  be  maintained  in  such  a  condition  that  water 
cannot  accumulate. 


MALARIA  179 

The  stock  pond,  so  common  in  the  vicinity  of  habitations 
in  some  sections,  is  a  menace  to  both  man  and  beast  and 
should  not  be  tolerated. 

The  care  of  streams  and  large  bodies  of  water  is  ordinarily 
simple,  since  these  rarely  threaten  sanitation  as  anopheles 
breeders.  Within  the  protected  area  the  banks  should  be 
cleared  of  dense  weeds  and  bushes,  eddies  prevented  where 
possible,  and  pools  along  the  edges  drained  into  the  channel. 

In  the  case  of  streams  that  get  very  low  after  the  rainy 
season,  leaving  a  chain  of  pools  along  the  river-bed,  these  pools 


Fig.  53. — An  ill-chosen  town  site  along  the  bayou. 

should  be  drained  into  each  other  and  an  attempt  made  to 
reestablish  a  flow  and  to  permit  of  scouring  and  the  access  of 
fish  from  the  larger  pools.  Where  the  pools  are  small  much 
water  can  be  gotten  rid  of  by  the  use  of  brooms. 

In  the  case  of  large  bodies  of  water  subject  to  overflow  the 
problem  is  more  difficult.  The  primary  effect  of  the  sub- 
merging of  land,  while  the  water  is  high,  is  to  diminish  malaria. 
The  secondary  effect,  after  the  waters  have  receded,  is  to  cause 
a  marked  increase.  The  effect  upon  malaria  of  inundations 
is  almost  yearly  observed  in  the  valleys  of  the  Nile,  of  the 


l8o  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


Fig.  54. — Anopheles  breed  among  the  cypress  knees. 


Fig-  SS- — ilany  breeding  places  are  left  upon  the  lowlands  after  the  overflow 
has  receded. 


Mississippi,  and  of  other  large  streams.  Levees,  dykes,  and 
other  engineering  means  of  large  dimensions  are  the  only 
remedies;  these  being  expensive  are  rarely  employed  merely 
for  sanitary  purposes. 

Marshes  and  swamps  when  too  extensive  to  be  filled  may 
be  effectively  drained.  The  drains  should  be  narrow,  of 
sufficient  depth  and  fall  to  drain  effectively,  and  may  be 
parallel,  crowfoot  fashion  or  otherwise,  as  best  suited  to  local 
conditions.     If    concreted    they    require    less    after-treatment 


Fig.   56. — A  stranded  skiff  containing  a  little  water  and  many  anopheles  wrigglers. 

and  may  be  cheaper  in  the  end.  If  not  concreted  they  should 
be  frequently  inspected  to  prevent  caving,  deposit,  or  filling 
with  vegetation.     The  tile  drains  are  usually  very  efficient. 

Large  swamps  in  the  vicinity  of  streams  have  been  rendered 
unfit  as  breeding  places  by  directing  the  course  of  the  stream 
through  them.  The  water  is  thus  given  a  current,  and  if  the 
stream  contains  much  mud  in  suspension  the  bed  of  the  marsh 
is  gradually  filled. 

Fresh-water  ponds  close  to  the  sea  have  been  successfully 
treated  by  filling  with  salt  water.     Water  strong  in  salt  is 


l82  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

not  attractive  for  breeding  purposes,  though  brackish  water 
may  harbor  numerous  larvae. 

The  rendering  innocuous  of  borrow  pits  along  railroad  lines 
is  difl&cult.  It  is  much  easier  to  prevent  the  stagnation  of 
water  during  the  construction  of  the  road  than  it  is  to  remedy 
the  defect  after  completion.  Filling  and  drainage  are  the  best 
correctives. 

The  de,struction  of  smaller  pools  and  puddles  is  usually  simple 
and  goes  far  toward  prophylaxis,  since  it  is  in  such  places  that 
anopheline  mosquitoes  breed  by  preference.     FiUing  is  by  far 


Tig    57  — The  cyclone  as  a  factor  m  malaria 

the  most  permanent,  hence  the  cheapest  and  most  desirable 
method  by  which  to  deal  with  these  collections  of  water.  Pools 
in  ditches  along  the  sides  of  roads,  wheel  ruts,  hoof  prints  of 
stock  in  soft  ground,  water  remaining  in  natural  inequalities 
in  the  ground  and  in  excavations  for  various  purposes  should 
be  assiduously  attended.  The  work  should  be  conducted  by 
one  who  is  familiar  with  the  rudimentary  principles  of  drainage. 
The  height  of  the  ground-water  is  very  intimately  asso- 
ciated with  the  prevalence  of  malaria,  since  the  quantity  of 
surface  water  depends  largely  upon  the  height  of  the  ground- 


water,  and  the  latter,  when  appearing  upon  the  surface,  is  a 
favorite  breeding  site  for  malarial  mosquitoes.  Hence,  meas- 
ures directed  toward  the  lowering  of  the  ground-water  are  of 
the  highest  efficacy  in  the  prophylaxis  of  malaria.  This  is 
evidenced  by  the  results  of  the  "tiling"  of  land  and  by  the  for- 
mation of  drainage  districts  for  the  reclamation  of  swamp 


Fig.   58. — This  pool,  fed  from  the  ice-plant,  contained  larvae  weeks  after  most 
other  pools  had  disappeared. 


lands.  Such  procedures  often  render  unnecessary  the  expendi- 
ture of  labor  or  money  for  the  removal  of  breeding  pools,  or 
other  antilarval  steps. 

In  certain  regions  where  the  hardpan  or  impervious  stratum 
is  responsible  for  a  high  ground- water  excellent  results  have 
been  obtained  by  boring  through  this,  thereby  allovvdng  the 


184  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

water  to   escape  into   the  permeable   earth   beneath.     These 
are  the  so-called  absorbing  wells. 

It  is  well  known  that  rice  culture  increases  the  malaria  of  a 
region  to  a  great  extent.  In  some  of  the  Oriental  countries 
the  crop  is  a  necessity,  but  in  regions  not  absolutely  dependent 
upon  the  crop  the  cultivation  of  rice  must  be  looked  upon  as 
an    evil.     In    fact,    some    governments    have    either    thrown 


Fig.  59. — Hunting  for  anopheles  larvie  along  the  levee. 

certain  restrictions  around  the  industry  or  have  altogether 
prohibited  it. 

The  eucalyptus  globulus  has  attained  considerable  reputa- 
tion as  a  preventive  of  malaria,  probably  from  a  belief  that 
it  absorbs  moisture  from  the  soil  and  renders  it  drier.  Recent 
experiments  in  Italy  have,  however,  shown  that  this  tree  has 
no  effect  in  decreasing  malaria,  and  that  it  even  affords  an 
excellent  shelter  for  anopheles  mosquitoes. 

Sunflowers  and  castor-oil  plants,  which  are  reputed  to  be 
beneficial  in  the  prophylaxis  of  malaria,  are  probably  devoid  of 
such  Afirtue. 


MALARIA  185 

There  are  circumstances  under  which  it  is  impossible  to  de- 
stroy the  breeding  pools.  Here  the  use  of  petroleum  is  indi- 
cated. This  oil  is  also  useful  in  antimalarial  campaigns  as  a 
temporary  measure  in  part  of  the  work  while  permanent 
means  are  being  employed  elsewhere. 

An  oil  should  be  chosen  which  spreads  rapidly  and  evaporates 
slowly.  The  refined  illuminating  oil  evaporates  readily,  hence 
is  too  expensive  for  work  on  a  large  scale.  The  most  suitable 
is  the  fuel  oil  or  blast-furnace  oil.  The  oil,  forming  a  film 
upon  the  entire  surface  of  the  water,  chokes  the  air  tubes  of 


Fig.   60. — An  embryo  scientist  seuixliing  for  aiiupliLks  larvs. 

the  larvae,  which  come  to  the  surface  to  breathe.  The  pupas 
expire  even  earlier  than  the  larvae,  since  they  require  more 
air.  Furthermore,  not  a  few  adult  female  mosquitoes  in  the 
act  of  oviposition  are  thereby  destroyed. 

The  pool  should  be  cleared,  as  far  as  possible,  from  weeds 
and  algae  which  interfere  with  the  spread  of  the  oil.  The  oil 
should  be  poured  from  a  watering  pot,  sprayed  by  means  of  a 
force  pump,  or  painted  over  the  surface  with  saturated  cloths 
tied  to  the  ends  of  sticks.  An  automatic  oiler  may  be  im- 
provised by  placing  a  barrel  of  oil  a  few  feet  above  the  water, 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


to  give  the  oil  the  necessary  spread,  and  having  a  perforation 
in  the  bottom  of  the  barrel  to  drop  about  twenty  times  to  the 
minute. 

The  quantity  of  oil  which  has  been  found  amply  sufficient 
is  I  ounce  for  each  15  square  feet  of  surface.  It  has  been 
estimated  that  a  barrel  of  oil  costing  only  a  few  dollars  is 
sufficient  to  cover  96,000  square  feet  of  surface. 

Evaporation,  rains,  and  winds  prevent  permanent  results, 
so  that  the  oiling  must  be  repeated.  Intervals  of  two  or  three 
weeks  are  the  proper  average,  and  certain  days  of  the  month 


Breeding  pools  in  the  borrow  pits  along  a  railroad. 


should  be  systematically  chosen.     It  is  best  to  begin  the  oil- 
ing in  the  spring  to  prevent  the  first  generation. 

Nearly  every  antiseptic  and  poison  has  been  employed  for 
the  destruction  of  mosquito  larvae.  The  aniline  derivatives 
are  valuable,  especially  that  known  as  Lardcide,  which  de- 
stroys also  fish  and  other  forms  of  Hfe  which  may  be  useful 
in  kilhng  larvae.  The  same  objection  applies  to  Fhinotas  Oil, 
a  cresol  combination,  and  saprol,  which  are  effective  larvi- 
cides.  Formahn,  corrosive  sublimate,  carbolic  acid,  and  lysol 
are  too  slow  in  their  effect  upon  larvae  to  be  of  practical  value. 


Permanganate  of  potash  has  proved  disappointing  in  all  trials 
made  of  it. 

Where  it  is  not  feasible  either  to  drain  or  oil  a  breeding  pool 
the  introduction  of  small  fish  has  been  practised  with  success. 
Certain  species  of  fish  prey  upon  the  eggs,  larvje,  and  pupae  of 
mosquitoes,  and  even  upon  adults  when  about  to  emerge  from 
the  pupal  shell  or  when  in  the  act  of  oviposition.  The  common 
top  minnows  {Gambusia  and  Fimdulus)  and  the  sun-fish  are 
excellent  for  this  purpose.  The  former  being  very  voracious 
and  top  feeders  are  especially  adapted  for  the  destruction  of 


— Breeding  pools  along  the  roadside. 


anopheles  larvae.  They  are  fast  breeders  and  resist  the  dry- 
ing of  pools  in  a  remarkable  degree.  Sticklebacks,  gold-fish, 
and  roach  are  also  larvivorous.  It  is  doubtful  whether  the 
common  German  carp,  on  account  of  its  feeding  habits,  is  of 
any  use  for  this  purpose.  The  tadpole  is  valueless  for  the 
destruction  of  larvae.  Ducks  destroy  many  larvae.  The 
larvae  of  the  dragon  fly,  the  water  boatman  and  the  hair  worm 
devour  mosquito  larvae. 

The  natural  enemies  of  adult  mosquitoes  are  few  and  prac- 
tically insignificant.  Dragon  flies,  night-hawks,  whip-poor- 
wills,  swallows,  bats,  and  certain  species  of  lizards  destroy  a 


l88  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

number  and  some  are  killed  by  parasitic  mites  and  a  small 
suctorial  fly. 

An  ideal  prophylaxis  destroys  the  breeding  pools  or  the 
aquatic  stages  of  mosquitoes,  but  remedies  against  the  adult 
insects  are  sometimes  necessary.  For  this  purpose  a  great 
variety  of  substances  have  been  tried.  One  of  the  most  primi- 
tive of  measures  is  the  smoldering  fire  of  chips,  rags,  and 
feathers,  to  be  seen  in  summer  twilight  to  the  windward  of 
nearly  every  negro  cabin. 

The  most  practical  means  are  the  fumes  of  burning  sulphur 


Fig.  63. — Breeding  pools  on  a  rice  farm. 


and  of  pyrethrum  powder.  The  room  to  be  fumigated  should 
be  made  as  nearly  air-tight  as  possible. 

Of  sulphur,  from  2  to  5  pounds  should  be  used  for  every  i  ,000 
cubic  feet  of  space.  Its  deleterious  effect  upon  metals  and 
delicate  fabrics  limits  its  use  somewhat.  Sulphur  dio.xide 
fumes  have  been  found  to  be  an  excellent  insecticide. 

The  room  should  be  kept  closed  for  several  hours  to  insure 
the  complete  extermination  of  the  insects. 

Pyrethrum  powder  may  be  burned  in  the  proportion  of  a  few 
ounces  to  a  pound  for  each  1,000  cubic  feet  of  space.     The 


mosquitoes  are  suffocated  by  the  fumes  and  must  be  swept  up 
and  destroyed. 

Formaldehyde  has  been  tried  and  found  wanting,  but  may 
be  effective  when  very  large  quantities  are  rapidly  liberated  in 
a  tight  room  with  few  hiding  places  for  the  insects. 

The  pulverized  leaves  and  stems  of  the  common  jimson  weed 
{Datura  stramonium),  mixed  with  saltpeter  and  burned  in 
the  proportion  of  5  ounces  to  1,000  cubic  feet  of  space, 
have  been  successfully  used  by  the  New  Jersey  Mosquito 
Commission. 

Chlorine  gas,  generated  by  adding  a  few  drams  of  sulphuric 
acid  to  an  ounce  of  chloride  of  lime,  is  said  to  be  efficient,  and 
burning  tobacco  leaves  is  useful. 


n.  MEASURES  DIRECTED  TOWARD  THE  DESTRUCTION  OF 
PARASITES 

Efforts  to  destroy  the  malaria  parasites  in  the  human  body 
assumes  two  modes.  The  first  consists  of  the  radical  cure  of 
the  malaria-infected  individual,  the  prevention  of  a  relapse, 
thereby  benefiting  the  individual  and  annihilating  a  source 
of  danger  to  the  community.  The  second  mode  consists 
of  the  administration,  to  persons  not  necessarily  infected, 
of  a  drug  which  destroys  the  parasite  soon  after  the  latter 
is  introduced  into  the  body,  before  the  incubative  stage  is 
completed. 

Cases  of  latent  and  atypic  malaria  are  of  greater  importance 
to  prophylaxis,  being  sources  of  greater  danger  to  communities 
than  are  typic  acute  cases.  The  duration  of  the  acute  attack 
is  short;  the  patient  is  apt  to  be  placed  under  relatively  favor- 
able conditions  and  to  receive  quinine;  he  does  not  wander  and 
disseminate  the  disease;  and  his  blood  may  contain  but  few 
sexual  forms  of  the  parasite.  On  the  other  hand,  the  subject 
of  latent  malaria  may  harbor  parasites  for  months  and,  the 
condition  being  unrecognized  or  ignored,  he  does  not  take 
quinine,  and  is  a  fountain  of  infection  in  diverse  places  and 
for  prolonged  periods. 

Koch  has  maintained  that  the  prompt  and  permanent  cure  of 


igo  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

all  acute  cases  of  malaria  and  the  systematic  search  for,  and 
appropriate  treatment  of,  all  latent  cases  in  a  region  will  re- 
sult in  the  extermination  of  the  disease  from  such  a  locality. 
This  is  theoretically  possible,  but  could  be  practised  only  in 
small  communities  under  perfect  control.  Nevertheless,  it 
is  certaintly  the  duty  of  physicians  to  endeavor  to  effect 
radical  cures  of  the  cases  which  come  under  their  observa- 
tion, a  duty  owed  not  only  to  the  patient  but  to  the  pubKc, 
and  such  efforts  will  go  far  toward  the  eradication  of  the 
disease. 

Quinine  Prophylaxis. — Theoretically  the  administration  of 
quinine  to  healthy  individuals  for  the  prevention  of  malaria 
is  not  an  ideal  method  of  prophylaxis,  for,  strictly  speaking,  it 
does  not  prevent  infection,  but  destroys  the  parasites  in  the 
incubative  stage  after  inoculation  into  the  human  body.  But 
no  one  method  satisfies  all  conditions;  each  has  its  advantages 
and  its  limitations,  and  frequently  two  or  more  methods  must 
be  employed  simultaneously. 

Quinine  prophylaxis  is  indicated  in  proportion  to  the  difficulty 
of  pursuing  more  permanent  methods.  It  is  valuable  where 
screens  and  bars  are  not  available,  as  in  camping,  marching, 
traveling,  or  where  the  occupation  takes  one  out  at  night. 
When  residents  of  non-malarial  countries  go  into  malarial 
locahties,  especially  in  the  rural  districts,  for  short  spaces 
of  time  quinine  is  a  most  valuable  prophylactic.  After  infec- 
tion is  known  to  have  occurred  quinine  is,  of  course,  essential 
not  only  as  a  cure,  but  as  a  preventive.  It  may  be  employed 
effectively  where  it  is  impossible  to  destroy  mosquitoes  or  as  an 
adjunct  to  other  measures. 

Numerous  experiences  attest  the  value  of  quinine  in  the  pro- 
phylaxis of  malaria. 

The  Society  for  the  Study  of  Malaria  in  Italy,  beginning 
prophylactic  experiments  on  a  small  scale  in  limited  areas, 
have  extended  their  practical  efforts  until  the  results  are  felt 
throughout  the  entire  country. 

Quinine  has  been  the  chief  reliance  of  this  organization. 

The  following  figures  give  the  malarial  mortality  in  Italy 
from  1900  to  1910: 


igi 


Year 

Deaths 

Year 

Deaths 

1900 

15,865 

1906 

4,871 

I901 

13,558 

1907 

4,160 

1902 

9,908 

1908 

3,463 

i9°3 

8,517 

1909 

3,533 

1904 

8,463 

1910 

3,619 

1905 

7,84s 

j» 

Fig.  64. 

Notwithstanding  the  favorable  experiences  recorded,  there 
are  disadvantages  in  the  employment  of  quinine  as  a  pro- 
phylactic. The  obstacles  are  much  greater  in  its  use  as  a 
public  measure  than  private. 

One  objection,  varying  considerably  with  individuals,  is 
cinchonism,  which  may  even  amount  to  very  unpleasant 
nervous  or  gastric  disturbances. 

To  be  efficient  as  a  preventive  of  malaria  quinine  must  be 
taken  in  sufficient  dose  during  the  entire  malarial  season. 
It  is  difficult  to  make  ignorant  people  realize  the  importance 
of  taking  treatment  during  several  months  to  prevent,  maybe, 
merely  a  chill,  and  few  governments  have  the  authority  to 
force  them  to  do  so.  No  permanent  results  are  to  be  ob- 
tained in  this  way  unless  all  take  the  drug  throughout  the 
malarial  season  and  all  cases  of  malaria  are  radically  cured. 

The  expense  of  public  prophylaxis  with  quinine  on  a  large 
scale  is  enormous,  in  fact,  in  some  instances  prohibitory. 
Money  spent  for  quinine  to  be  given  in  inadequate  doses  at 
irregular  intervals  is  wasted. 

The  size  of  the  dose  and  the  interval  at  which  the  prophylactic 
is  administered  are  of  the  utmost  importance.  Very  varying 
quantities  have  been  employed  at  different  intervals,  but  the 
estabhshed  methods  have  about  settled  down  to  that  described 
below : 

The  method  canonized  by  Koch  consists  in  giving  i  gram 
of  quinine  every  sixth  and  seventh  day,  seventh  and  eighth, 
eighth  and  ninth,  or  ninth  and  tenth  day,  according  to  the 
danger  of  infection.  This  manifestly  leaves  several  intervening 
days   in   v/hich   there  is   no   quinine  in   the   circulation.     In 


192  ENDEMIC  DISEASES  OE  THE  SOUTHERN  STATES 

localities,  therefore,  in  which  estivo-autumnal  malaria  is  prev- 
alent, the  shorter  interval  of  administration  should  be  pre- 
ferred on  account  of  the  shorter  period  of  incubation  of  this 
form  of  malaria. 

The  Koch  method,  every  sixth  and  seventh  day,  has  been 
satisfactory  in  my  hands. 

Prophylactic  quinine  should  be  continued  for  two  or  three 
months  after  leaving  a  possible  source  of  infection,  even  if  the 
disease  has  not  been  contracted,  and,  in  the  latter  event,  for 
yet  a  longer  period. 

Combinations  in  pill  form  of  quinine,  iron,  and  arsenic, 
known  as  antimalarial  pills,  are  valuable  as  tonics  and  are 
mildly  prophylactic.  They  do  not,  however,  contain  sufficient 
quinine  to  be  reliable  prophylactics,  at  least  in  this  region. 
Such  pills,  Grassi's  esanophele  pills,  were  tried  in  comparison 
with  sulphate  and  hydrochlorate  of  quinine  by  the  Italian 
Antimalaria  Society  and  found  to  be  less  efficient.^-" 

Arsenic,  so  long  vaunted  as  an  antimalarial,  has  been  thor- 
oughly tried  and  abandoned. 

Tea,  coffee,  and  lemons  have  very  slight  preventive  virtue, 
if  any  at  all. 

m.  MEASURES  TO  PREVENT  THE  ACCESS   OF  MOSQXHTOES 

Exclusion  of  Mosquitoes. — The  prophylactic  value  of  ex- 
cluding mosquitoes  is  in  proportion  to  the  number  of  an- 
ophelines  and  the  proximity  of  infected  persons. 

A  properly  protected  house  should  have  every  door  and 
window  screened.  In  some  localities  it  is  advisable  to  cover 
even  the  chimneys  with  wire  netting.  Doors  should  be  pro- 
vided with  springs  to  necessitate  closure.  Where  mosquitoes 
are  plentiful  and  a  door  is  much  used,  a  double  door,  with 
an  intervening  vestibule,  after  the  manner  of  the  Italians  is 
to  be  preferred.  A  screened  porch  permits  of  sitting  in  the 
air  in  the  evening  when  it  would  be  dangerous  to  do  so  otherwise. 

The  selection  of  the  gauze  for  screens  is  of  the  highest 
importance.  The  mesh  of  the  wire  netting  often  used,  No. 
12,  is  too  large,  permitting  small  mosquitoes  to  pass.  None 
should  be  used  with  fewer  meshes  than  eighteen  to  the  inch. 


MALARIA  193 

In  the  absence  of  wire  gauze,  cotton  mosquito  netting  may 
be  employed,  but,  being  frail,  soon  becomes  torn  and  useless. 

Persons  whose  occupations  keep  them  out  at  night  in  highly 
malarial  places,  as  watchmen  and  others,  should  be  protected 
with  veils  and  with  leather  gloves  having  gauntlets. 

The  mosquito  bar  is  indispensable  in  malarial  countries. 
Besides  being  very  effective  when  properly  adjusted,  it  is  the 
most  inexpensive  of  all  prophylactic  methods. 

As  with  every  other  method  for  the  prevention  of  malaria, 
screens    have    certain    shortcomings.     It    is    evident    that    if 


Fig.   65. — A  model  of  house  screening. 

malaria  is  to  be  eradicated  by  these  means  from  a  locality 
every  house  should  be  screened,  otherwise  only  those  in  the 
protected  houses  would  be  exempt,  and  only  so  long  as  they 
remain  in  such  houses.  It  is  out  of  the  question  in  many 
malarial  places  to  consider  the  screening  of  all  the  houses,  both 
on  account  of  the  expense  and  because  of  the  poor  construction 
of  many  of  them,  permitting  mosquitoes  to  enter  through 
crevices  and  other  openings.  The  fact  that  screens  offer  a 
shght  hindrance  to  the  free  circulation  of  air  in  hot  countries 
is  of  little  moment  in  the  face  of  the  benefits  derived  from  their 


194  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

use,  and  they  must  be  considered  as  one  of  the  most  effective 
means  of  private  prophylaxis. 

Of  local  applications  to  drive  away  mosquitoes  many  sub- 
stances have  been  tried,  particularly  the  essential  oils,  of  which 
the  oils  of  citronella  eucalyptus  and  lavender  are  probably 
the  most  efhcacious.  Petroleum,  infusion  of  quassia,  naph- 
thaline, powdered  sulphur,  camphor,  garlic,  the  oils  of  cloves, 
tar,  pennyroyal,  chrysanthemum,  and  anise  have  been  em- 
ployed with  varying  degrees  of  success. 

In  India  the  punka  is  employed  to  keep  the  air  in  motion, 
and  for  this  reason  is  found  to  be  of  service  in  driving  away 
mosquitoes.  The  electric  fan  has  this  effect  also,  but  for  ob- 
vious reasons  should  not  be  employed  for  this  purpose  during 
sleep. 

The  value  of  smoke  against  mosqviitoes  is  well  known,  though 
it  is  not  always  entirely  effective.  I  recall  an  occasion  while 
on  an  island  off  the  Gulf  coast  of  Florida  where  smoke  was  of 
no  avail  against  the  terrific  onslaught  of  bloodthirsty  mos- 
quitoes, and  it  became  necessary  to  bury  myself  up  to  the  neck 
in  the  sand  and  to  cover  my  head  with  a  coat. 

Isolation  of  the  malarial  patient  is  as  truly  indicated  as  in 
yellow  fever,  both  diseases  being  conveyed  in  the  same  manner. 
Mosquitoes  must  become  infected  before  they  can  infect  man; 
breaking  the  vicious  circle  at  this  point  would  extirpate  malaria. 
Isolation  is  demanded  not  only  for  the  good  of  the  community, 
but  to  prevent  reinfection  of  the  patient  v/ho  should  be  con- 
fined under  a  well-adjusted  bar  until  a  radical  cure  is  effected. 
It  is  not  to  be  expected,  however,  that  as  much  can  be  ac- 
complished from  the  isolation  of  malaria  as  from  isolation  of 
yellow  fever.  Many  cases  of  malaria  entirely  escape  medical 
treatment,  and  a  malarial  subject  may  be  a  source  of  infection 
for  a  year  or  more,  while  yellow  fever  is  infectious  for  only  a 
few  days. 

Since  it  has  become  evident  that  so  great  a  proportion  of  the 
inhabitants,  especially  the  children  of  tropic  countries,  harbor 
malarial  parasites  in  the  blood,  segregation  of  the  whites  from 
the  natives  has  been  proposed  and  in  some  instances  practised 
with  success.     While  the  question  is  of  some  import  in  this 


MALARIA  19s 

country,  the  negro  'quarters  in  most  of  our  towns  are  fairly 
well  defined  from  those  of  the  white.  Upon  the  premises  the 
householder  should  see  that  his  servants'  quarters  are  as 
thoroughly  screened  as  his  own.  In  the  choice  of  camp  sites 
native  houses  should  be  avoided  beyond  the  limit  of  flight  of 
mosquitoes,  if  possible. 

Great  good  is  being  accomplished  in  the  prophylaxis  of 
tuberculosis  by  education,  keeping  the  main  facts  in  the  etiology 
and  prevention  constantly  before  the  eyes  of  the  people.  So 
much  cannot  be  expected  from  malaria  on  account  of  the  ig- 
norance and  carelessness  of  the  class  and  race  of  people  most 
scourged,  but  undoubtedly  some  good  may  accrue  from  this 
method.  The  Europeans,  at  home  and  in  their  colonies,  have 
obtained  some  results  in  the  prophylaxis  of  malaria  by  teach- 
ing the  people  the  elements  of  the  cause  and  prevention  of  the 
disease. 

Lectures,  illustrated  by  stereopticon  views,  are  held  publicly. 
Publications  in  simple  language,  in  the  form  of  circulars  and 
tracts,  and  even  appropriately  illustrated  postcards  are  scattered 
broadcast.  The  Italian  Society  for  the  Study  of  Malaria  has 
distributed  about  two  million  of  these  circulars.  The  prin- 
ciples of  prophylaxis  are  instilled  into  the  minds  of  the  school 
children,  and  made  attractive  and  impressed  by  means  of 
illustrated  charts.  The  lay  press  has  been  used  to  advantage. 
With  such  means  the  formation  of  an  antimalarial  league  can 
do  much  for  a  community.  A  little  can  be  accomplished  by 
education,  and  this  little  should  not  be  neglected. 

To  be  thorough,  malaria  prophylaxis  should  be  handled  by 
the  Government.  Destruction  of  the  breeding  places  of  the 
mosquitoes,  which  is  by  far  the  most  radical  method,  is,  in 
many  instances,  too  expensive  to  be  done  by  individuals.  The 
formation  of  drainage  districts,  the  expenses  of  which  are 
paid  by  those  benefited,  is  an  effective  plan,  and  so  enhances 
the  value  of  real  estate,  from  both  agricultural  and  sanitary 
standpoints,  that  there  should  be  no  opposition. 

It  should  be  the  duty  of  the  authorities  of  every  malarial 
country  to  remove  the  duty  from  quinine  and  to  maintain  a 
high  standard  of  purity  and  a  low  price. 


196  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Private  prophylaxis  consists  of  measures  having  reference  to 
the  person  and  to  the  premises.  Personal  prophylaxis  is 
synonymous  with  proper  hygiene.  Suitable  food,  water,  and 
clothing  are  essential.  Regular  hours  must  be  kept,  and 
constipation,  chilling  of  the  body,  and  excess  of  all  kinds 
must  be  avoided.  Prophylactic  quinine  is  not  constantly 
necessary  for  residents  if  the  premises  are  in  proper  condi- 
tion, but  is  suitable  for  strangers  and  under  conditions  where 
mosquitoes  cannot  be  excluded.  Persons  sleeping  upstairs 
are  less  liable  to  infection  than  those  upon  the  first  floor. 

Pools  are  to  be  filled,  drained,  or  oiled,  and  vessels  emptied. 
It  has  been  suggested  that  a  tub  of  water  be  kept  on  the  place 
to  tempt  mosquitoes  to  breed,  and  that  this  be  emptied  every 
few  days.  Stock  ponds  should  be  drained,  oiled,  or  stocked 
with  fish.  The  houses  should  be  thoroughly  screened,  and 
where  these  are  not  effective,  or  if  infection  occurs,  bars  must 
be  employed. 


CHAPTER  Vni 
TREATMENT  OF  MALARIA 

While  quinine  is  more  nearly  speciiic  than  any  other  known 
drug,  it  has  imitations  and  while  the  clinical  manifestations  of 
malaria  usually  subside  readily  after  quinine,  a  radical  cure  is 
sometimes  difficult.  A  few  grains  a  day  wiU  relieve  many  cases, 
though  a  dram  a  day  will  not  save  some  patients.  A  few  of 
the  sequelce  of  malaria  are  but  little,  if  at  all,  influenced  by 
quinine. 

Among  the  alkaloids  of  cinchona  bark  quinine  is  the  one 
now  generally  used.  The  following  table  shows  the  alkaloidal 
strength  of  the  various  salts  of  quinine,  as  well  as  their  solubility: 


Quinine,  anhydrous 

Quinine  acetate 

Quinine  bimurite  (or  acid  liydrochloride) 

Quinine  bisulphate 

Quinine  citrate 

Quinine  liydrobromide 

Quinine  lactate 

Quinine  hydrocUoride , 

Quinine  salicylate 

Quinine  sulphate 

Quinine  tannate,  about 

Quinine  valerianate 

Euquinine 


1,75° 

Slightly 

less  than  weight 

8.S 

820- 

40 

10 

18 

77 

720 

800 


Absorption  and  Elimination  of  Quinine. — Most  of  the  salts 
are  readily  absorbed  from  the  stomach.  It  has  been  shown, 
however,  that  the  tannate  is  more  largely  absorbed  from  the 
small  intestine. 

197 


igS  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

The  rapidity  of  absorption  varies  with  the  different  salts, 
and  is  estimated  by  the  length  of  time  required  to  appear  in 
the  urine.  The  time  from  the  administration  of  the  drug 
until  it  begins  to  appear  in  the  urine  is  represented  as  follows: 

Hydrochloride 15  minutes. 

Bisulpliate 30  minutes. 

Sulphate 45  minutes. 

Acetate 30  minutes. 

Citrate 30  minutes. 

Tannate 3  hours. 

The  method  of  administration  of  quinine  also  influences  the 
rapidity  with  which  it  is  absorbed. 

Given  by  the  mouth,  a  highly  soluble  salt  will  begin  to  appear 
in  the  urine  within  fifteen  to  thirty  minutes,  and  is  eHminated 
in  the  greatest  quantity  within  three  to  twelve  hours. 

While  it  is  a  widely  prevalent  behef  that  the  soluble  salts  of 
quinine  are  much  more  rapidly  and  completely  absorbed 
from  the  stomach  than  are  the  insoluble  preparations,  experi- 
ments show  that  such  is  not  the  case. 

Giemsa  and  Schaumann^^-  observed  that  the  average  per- 
centage excreted  within  the  first  twenty-four  hours  after  ad- 
ministration of  a  soluble  salt  of  quinine  was  22.9  per  cent., 
while  with  an  insoluble  salt  it  was  24.33  P^^  cent.,  and  they 
conclude  that  the  salts  of  quinine,  hardly  soluble  in  water, 
are  at  least  as  energetically  absorbed  from  the  digestive  tract 
as  the  soluble  ones. 

The  results  of  chnic  experience  with  euquinine  and  the 
tannate  of  quinine  fully  support  such  a  conclusion. 

Employed  hypodermically  the  rapidity  and  thoroughness 
of  absorption  depends  upon  the  solubility  of  the  salt  and  the 
concentration  of  the  solution.  The  latter  is  of  the  utmost 
importance,  since,  no  matter  how  soluble  the  salt,  if  given  in 
strong  solution  it  will  not  be  absorbed. 

The  rate  of  excretion  after  injection  of  solutions  of  bimuriate 
of  quinine,  i  gram  to  10  c.c.  of  water  and  i  gram  to  i  c.c.  of 
water,  is  recorded  in  the  following  tables,  respectively  :^^^ 


199 


Total  Daily  Elimination  Estimation  in  Per  Cent,  of  Anhydrous 
Quinine 


Number  of  patient 


I  :io 

One  day. . . . 
Two  days. . . 
Three  days. 


21.  o 

26.  2 


Average 

Average  of  three  cases,  23.3  per  cent. 


23.6 


One  day. . . . 
Two  days. . 
Three  days. 


10.3 
16.3 
18.2 


Average 

Average  of  three  cases,  11. 8  per  cent. 


24.1 
24.9 
26.9 

25-3 


iS-i 
193 


3 
19.8 
22.0 


8.3 

S-2 

£  .  2 


Mariani"'  found  that  after  the  injection  of  i  gram  of  the 
bimuriate  of  quinine  dissolved  in  10  c.c.  of  water  the  maximum 
excretion  occurred  between  the  sixth  and  the  twelfth  hours, 
while  after  the  injection  of  the  same  quantity  of  the  salt 
dissolved  in  2  c.c.  of  water  this  period  occurred  between  the 
ninth  and  the  eighteenth  hours. 

As  compared  with  the  oral  administration  of  quinine  the 
hypodermic  method  has  been  ascertained  to  be  followed  by 
the  absorption  of  a  smaller  proportion  of  the  drug.  The  pro- 
portion is,  according  to  Giemsa  and  Schaumann,  38.5:17.5; 
according  to  Mariani,  45.63  :  31.86,  and  according  to  Schmitz 
27.7  :  16. 1. 

After  intravenous  administration  quinine  has  been  detected 
in  the  urine  in  ten  minutes. 

Injected  into  the  rectum  quinine  appears  in  the  urine  in 
twenty  to  twenty-five  minutes.  On  account  of  the  tenesmus 
which  quinine  solutions  are  prone  to  produce  when  introduced 
into  the  rectum,  experiments  are  not  very  numerous,  but  those 
performed  show  that  the  drug,  even  in  a  highly  soluble  form, 
is  much  less  easily  absorbed  than  when  given  orally. 


200  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Besides  with  the  urine,  quinine  is  excreted  with  the  feces, 
the  milk,  the.  sweat,  the  tears,  pathologic  transudates  and 
exudates,  the  amniotic  fluid,  and  the  first  urine  of  the  new- 
born children  of  cinchonized  mothers. 

Action  of  Quinine  upon  the  Malaria  Parasites. — Binz,  in 
1867,  was  the  first  to  assume  that  the  effect  of  quinine  in 
malaria  was  due  to  its  action  as  a  protoplasmic  poison  upon  the 
organisms  which  he  beUeved  to  be  the  cause  of  the  disease. 
This  conclusion  was  reached  from  a  knowledge  of  the  action 
of  quinine  upon  infusoria. 

In  1881  Laveran  found  that  the  parasites  were  killed  by  the 
addition  of  i  :  10,000  solution  of  quinine,  and  concluded  that 
"it  is  because  it  destroys  the  parasites  that  quinine  causes  the 
disappearance  of  the  manifestations  of  paludism." 

It  is  well  known  that  the  sexual  forms  of  the  malaria  para- 
sites are  very  resistant  to  quinine,  persisting  in  the  blood  for 
weeks  and  months  despite  the  liberal  use  of  quinine. 

While  young  and  half-grown  tertian  and  quartan  gametes 
are  sometimes  destroyed  by  quinine,  those  of  the  estivo- 
autumnal  variety  are  exceedingly  difficult  to  kill.  In  fact,  it 
has  been  maintained  that  the  administration  of  quinine  to 
patients  harboring  only  the  asexual  forms  favors  the  develop- 
ment of  crescents. 

Macrogametes  are  more  resistant  to  the  effects  of  quinine 
than  are  the  microgrametocytes.  This  may  possibly  be  due 
to  the  thicker  protoplasmic  body  of  the  former,  and  explains 
the  difficulty  of  interrupting  the  parthenogenetic  cycle,  the  cycle 
of  chronic  or  latent  malaria. 

Binz  observed  that  infusoria  were  stimulated  to  increase 
movement  by  quinine.  The  same  has  been  noted  with  the 
parasites  of  malaria. 

That  small  doses  of  quinine  are  able  to  arouse  latent  malaria 
is,  in  my  opinion,  unquestionable.  This  can  be  explained 
satisfactorily  only  by  assuming  that  quinine  stimulates  the 
parthenogametes  into  a  compensatory  reproduction. 

It  is  the  uniform  result  of  experience  that  the  stage  of  the 
parasite  most  susceptible  to  the  action  of  quinine  is  the  mero- 
zoite,  the  spore  before  it  has  assumed  the  protection  of  the  red 


cell.  Hence  it  is  desirable  to  have  in  the  blood  as  strong  a 
solution  of  quinine  as  possible  at  the  time  of  sporulation,  that 
the  young  parasites  may  be  born  into  a  toxic  medium. 

The  exact  manner  in  which  quinine  destroys  the  parasite  of 
malaria  is  not  certain.  Whether  it  acts  as  a  direct  poison  to  the 
parasite,  or  by  stimulating  phagocytosis,  or  by  increasing 
the  fluorescence  of  the  blood,  or  by  forming  indiges- 
tible combinations  with  the  blood  elements,  has  not  been 
determined. 

Centra-indications  to  the  Use  of  Quinine.^ — The  mere  state- 
ment of  the  patient  that  he  is  unable  to  take  quinine  should 
constitute  no  bar  to  the  use  of  the  specific.  The  history  of 
the  invariable  sequence  of  very  severe  skin  manifestations 
should  perhaps  lead  the  physician  to  employ  one  of  the  sub- 
stitutes for  quinine. 

Cardiac  depression  and  dyspnea  are  decided  contra-indica- 
tions  to  the  administration  of  the  drug. 

The  treatment  of  malaria  complicating  pregnancy  is  essen- 
tially the  same  as  under  other  conditions.  A  fear,  probably 
more  fancied  than  real,  of  the  oxytocic  properties  of  quinine 
is  widely  prevalent,  but  of  the  dilemma,  malaria  or  quinine, 
the  latter  is  certainly  the  shorter  horn.  The  pregnant  patient 
runs  far  less  risk  of  abortion  with  rational  quinine  treatment 
than  without.  Malaria  during  pregnancy  is  notoriously 
stubborn,  and,  while  the  attack  should  be  treated  with  the 
smallest  doses  necessary  to  effect  a  prompt  cure,  systematic 
and  prolonged  quinine  prophylaxis  is  necessary  to  prevent  re- 
currences. If  labor  pains  have  begun,  opium  should  be  ad- 
ministered with  the  quinine. 

The  history  of  hemoglobinuric  fever  is  no  contra-indication 
to  the  use  of  quinine.  While  the  administration  of  the  drug 
is  sometimes  the  occasion  of  an  outbreak  of  blackwater  fever, 
the  latter  is  generally  due  to  too  little  quinine  rather  than  to 
too  much.  Nor  is  it  advisable  to  restrict  the  size  of  the  dose 
unnecessarily  through  fear  of  an  attack,  since  it  has  been 
shown  that  the  amount  of  quinine  is  of  little  importance  in  the 
etiology,  very  small  quantities  being  as  prone  to  occasion 
the  attack  as  moderate  amounts. 


202  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Choice  of  Preparation. — This  is  influenced  by  the  age  of  the 

patient,  the  mode  of  administration,  the  severity  of  the  attack 
and  other  factors. 

The  sulphate,  on  account  of  its  cheapness  and  the  ease  with 
which  it  is  obtained,  is  widely  employed.  I,  however,  now 
rarely  employ  it,  and  then  only  in  suspension  in  syrup  of  yerba 
santa  for  children.  It  is  probable  that  it  gives  rise  to  more 
gastro-intestinal  and  nervous  disturbances  than  any  other 
salt  of  quinine,  and  it  is  these  manifestations  produced,  as  a 
rule,  by  this  salt,  which  cause  so  many  persons  to  say  to  the 
physician  that  they  cannot  take  quinine. 

The  bisulphate,  the  hydrobromide  or  bromide,  and  the 
hydrochloride  are  useful  preparations,  being  easily  dissolved  and 
readily  absorbed. 

The  bimuriate,  or  acid  hydrochloride,  or  dihydrochloride  is 
the  most  valuable  salt  of  quinine.  Its  great  solubility  adapts 
it  for  solution  to  be  given  by  mouth,  by  rectum,  intramus- 
cularly, or  intravenously. 

Euquinine,  or  quinine  ethyl  carbonate  has  been  thoroughly 
tried  and  has  given  satisfactory  results  in  my  hands.  Being 
practically  tasteless,  it  is  easily  administered,  either  in  powder 
or  suspended  in  a  neutral  syrup,  to  children.  An  acid  with  the 
drug  or  immediately  following  develops  a  bitter  taste.  The 
objections  to  the  preparation  are  its  expense  and  the  fact  that 
it  is  patented. 

The  tannate  of  quinine,  on  account  of  its  small  proportion 
of  alkaloid  and  slight  solubility,  has  been  until  recently  only 
rarely  employed  in  the  therapy  of  malaria.  The  Italian 
Government,  in  an  effort  to  supply  a  tasteless  salt  of  quinine 
for  children,  has  been  dispensing  tannate  of  quinine  in  the 
form  of  chocolate  confections.  A  commission  of  members  of 
the  Superior  Council  of  Health,  appointed  to  investigate  the 
results  obtained  by  this  method  of  administration,  reported 
adversely.  They  concluded  that  the  tannate  of  quinine  is 
one  of  the  most  insoluble  preparations  of  quinine,  and  that  it  is 
weakly  and  slowly  acted  upon  by  the  digestive  fluids;  that  the 
fat  of  the  cocoa  retards  the  action  of  the  digestive  fluids  upon 
the  quinine  and  causes  it  to  deteriorate  under  the  influence 


MALARIA  203 

of  the  air.  This  report  was  the  occasion  of  a  unanimous 
remonstrance  by  numerous  physicians  who  obtained  excellent 
results  from  the  use  of  the  tannate. 

My  own  experience  with  this  salt,  together  with  the  re- 
ports of  the  Italian  physicians,  leads  to  the  following  con- 
clusions : 

1.  The  tannate  of  quinine  is  almost  completely  absorbed 
from  the  alimentary  tract. 

2.  It  is  more  slowly  absorbed  and  more  slowly  eliminated 
than  the  other  salts  of  quinine,  and  remains  in  the  system 
longer. 

3.  A  small  quantity  only  of  the  salt  is  acted  upon  by  the 
gastric  juice,  but  is  largely  absorbed  from  the  bowel  after  con- 
tact with  the  bile  and  pancreatic  juice. 

4.  It  is  not  absorbed  when  injected  into  the  rectum. 

5.  It  is  better  tolerated  by  the  stomach,  intestines,  and 
nervous  system  than  the  sulphate. 

6.  The  clinic  results  with  the  tannate  of  quinine  are  entirely 
satisfactory. 

7.  Being  nearly  tasteless,  it  is  especially  adapted  to  the 
treatment  of  malaria  in  children. 

8.  It  has  a  good  effect  upon  diarrhea  and  dysentery  com- 
plicating malaria. 

9.  It  is  several  times  less  expensive  than  any  other  tasteless 
preparation  of  quinine. 

Methods  of  Administration  of  Quinine. — Administration 
by  the  Mouth. — In  simple  cases  of  malaria,  administration  of 
quinine  by  the  mouth  is  the  rule;  by  other  methods  the  ex- 
ception. It  is  probable  that  ninety-nine-one-hundredths  of 
the  quinine  consumed  is  given  by  the  oral  route. 

There  are  those,  not  objecting  to  the  taste  of  quinine,  who 
will  take  it  in  the  powdered  form;  in  fact,  it  is  a  common 
method  among  the  Southern  negroes  to  lick  it  from  the  palm 
of  the  hand.  The  taste  is,  however,  so  repulsive  to  most 
persons  that,  with  the  exception  of  the  tannate  and  euquinine, 
it  must  be  given  in  some  other  form. 

The  same  objection  applies  to  giving  the  drug  in  solution, 
though  this  is  unquestionably  the  most  reliable  form  in  which 


204  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

to  give  it  by  the  mouth,  but  for  obvious  reasons  it  cannot  be 
so  extensively  employed  in  this  manner  in  private  practice. 
The  solution  is  more  quickly  and  completely  absorbed.  The 
bimuriate  and  the  bisulphate  are  the  salts  most  suitable  for 
solution,  but  if  neither  of  these  is  at  hand  the  sulphate  may  be 
employed  by  adding  a  drop  of  dilute  hydrochloric  or  sulphuric 
acid  for  each  grain  of  the  quinine. 

The  most  eificient  vehicle  for  disguising  the  taste  of  the 
sulphate  of  quinine  is  the  syrup  of  yerba  santa.  Two  grains 
of  quinine  to  the  dram  of  the  syrup  is  the  suitable  proportion. 
Syrup  of  chocolate,  fluidextract  of  licorice,  ginger,  coffee,  milk, 
honey,  olive  oil,  and  other  media  have  been  recommended,  but 
are  far  from  satisfactory.  Acid  fruit  juices  and  syrups  usually 
enhance  the  bitter  taste. 

Where  prejudice  against  quinine  makes  it  necessary  to  dis- 
guise the  appearance  of  the  drug,  this  may  be  accomplished 
effectively  by  adding  a  small  quantity  of  charcoal,  turmeric, 
or  methylene-blue  to  the  bimuriate,  bisulphate,  or  other  salt. 

Pills  and  tablets  are  convenient  to  administer  and  not  un- 
pleasant to  take,  but  cannot  be  rehed  upon.  The  coating 
often  becomes  so  hard  as  to  make  solution  difficult  or  im- 
possible. I  have  several  times  seen  quinine  given  in  this  form 
pass  from  the  bowel  wholly  unaffected.  Pills  and  tablets 
should  not  be  given  when  capsules  can  be  obtained.  Capsules, 
when  fresh,  are  easily  dissolved.  If  there  is  any  doubt  as  to 
their  quality  they  may  be  punctured  several  times  in  each 
end  with  a  pin,  or  may  be  followed  by  a  few  drops  of  a  dilute 
mineral  acid. 

In  the  absence  of  capsules  quinine  has  been  rolled  in  a 
little  ball  with  cigarette  paper.  Absorption  is  extremely  slow 
and  uncertain,  and  this  method  should  not  be  resorted  to. 

The  tannate  of  quinine  has  been  compounded  with  the 
chocolate  confection  for  administration  to  children,  and  in  this 
form,  if  reliably  made,  is  readily  taken,  and  in  sufficient  dose 
is  efficient. 

Hypodermic  Method. — The  most  suitable  salt  of  quinine  for 
injection  in  unquestionably  the  bimuriate.  The  tablets  of 
bimuriate   of   quinine   and   urea   are   convenient   and   insure 


MALARIA  205 

accurate  dosage.  The  3-grain  tablets  contain  approximately 
2)4,  grains  of  the  quinine  salt. 

The  advantages  of  giving  quinine  by  the  needle  in  pernicious 
malaria  are  obviously  being  able  to  administer  it  to  patients 
unable  to  swallow  or  to  retain  it,  and  the  certainty  and  prompt- 
ness of  absorption.  Nevertheless,  these  great  benefits  are 
somewhat  discounted  by  the  bad  results  which  sometimes 
appear.  Formerly  tetanus  was  to  be  feared.  But  there  are 
other  consequences  which,  while  not  so  deadly,  are  more  com- 
monly met.  Nodules,  necrosis,  sloughing,  and  abscess  forma- 
tion are  referred  to. 

These  results,  however,  should  not  prevent  the  use  of  quinine 
injection  in  the  treatment  of  pernicious  malaria,  as  such 
effects  are,  in  a  great  measure,  preventable.  To  this  end  there 
are  three  measures  of  importance:  first,  asepsis;  second,  dilute 
solutions;  and  third,  deep  injections. 

The  first  is  at  the  present  day  probably  the  least  often 
neglected,  as  most  physicians  realize  the  importance  of  sterili- 
zation, and  a  spoonful  of  water  and  a  few  matches  are  suf- 
ficient to  effect  it  on  the  part  of  the  solution  and  needle,  and 
soap  and  water  are  almost  omnipresent. 

The  necessity  of  employing  a  chlute  solution  has  been  all  but 
ignored.  Nearly  all  writers  on  the  subject  lay  great  stress  on 
the  need  of  asepsis,  but  with  few  exceptions  never  even  mention 
the  evils  of  too  concentrated  solutions.  Strong  solutions  of 
quinine  injected  into  the  tissues  cause  a  wall  of  necrosis  around 
the  solution,  preventing  absorption  and  paralyzing  phago- 
cytosis, resulting,  even  if  the  solution  is  sterile,  in  nodes  or 
ugly  chemic  sloughs.  It  is  in  all  probability  this  chemic 
irritation  of  the  cells  which  allows  of  bacterial  infection  follow- 
ing the  injections  of  solutions  not  properly  sterilized,  and,  no 
matter  how  sterile  the  solution,  if  too  concentrated,  a  nodule 
or  chemic  slough  is  apt  to  result.  Witness  the  frequency  with 
which  unsterilized  solutions  of  morphine  and  other  drugs  are 
given  without  the  slightest  bad  consequence. 

For  injection  purposes  the  following  formula  is  most  suitable: 

Quinine  bimuriate i  gm.  (gr.  xv) 

Water 10  c.c.  (dr.  iise). 


2o6  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

As  much  of  this  as  needed  may  be  injected  in  one  or  several 
locations. 

The  solutions  should  not  be  injected  hypodermically,  but 
intramuscula.rly,  since  in  the  latter  location  the  injection  is 
more  certainly  absorbed,  is  less  apt  to  cause  induration  and 
abscess,  and  is  less  painful.  In  some  cases  of  pernicious  malaria 
the  superficial  circulation  is  very  poor,  absorption  corre- 
spondingly inadequate,  and  necrosis  almost  inevitable  if  the 
quinine  is  not  deeply  injected.  In  a  case  of  algid  malaria  in 
my  practice  where  the  quinine  was  given  hypodermically  the 
site  of  injection  began  to  turn  blue  within  ten  minutes  and  was 
almost  black  within  two  hours. 

The  initial  dose  should  ordinarily  be  15  grains.  Afterward 
from  5  to  10  grains  should  be  injected  every  six  to  eight  hours 
as  long  as  the  symptoms  demand  it.  For  children  under  five 
years  the  first  dose  may  be  ij^  grains  for  each  year  of  age. 

Most  of  the  continental  writers  recommend  the  Pravaz  or 
Luer  syringes,  with  platin-iridium  needles,  but  the  ordinary 
antitoxin  syringe  answers  as  well.  A  soft-rubber  tubing 
connection  between  the  needle  and  the  nipple  of  the  syringe  is 
advantageous,  as  it  may  prevent  the  breaking  of  a  needle  in  a 
struggling  patient.  One  of  these  syringes,  a  small  sterilizing 
pan,  and  alcohol  lamp  do  not  occupy  much  space,  and,  being 
almost  indispensable  in  these  cases,  should  be  easily  accessible 
during  the  malaria  season  to  the  physician  in  a  malarial  lo- 
cality, who  often  sees  these  cases  miles  from  his  ofifice,  when 
time  is  a  matter  of  life  and  death.  The  ordinary  hypodermic 
syringe  may  be  used  in  an  emergency,  but  to  use  a  sufficient 
quantity  of  a  properly  diluted  solution  a  number  of  injections 
have  to  be  made. 

The  best  location  for  injection  is  in  the  gluteal  region  well 
above  the  ischial  tuberosities,  though  the  interscapular  region 
is  often  chosen. 

The  technic  of  intramuscular  injections  of  quinine  may  be 
summarized  in  these  precautions:  Have  the  solution  freshly 
made,  thorough,  dilute,  and  sterile;  render  the  syringe  and 
the  injection  site  aseptic;  insert  the  needle  into  muscular  tissue, 
and  avoid  breaking  the  needle. 


MALARIA  207 

Intravenous  Method. — In  1890  Bacelli"'*'*  introduced  the 
intravenous  administration  of  quinine  in  the  treatment  of 
pernicious  malaria,  claiming  thereby  to  have  reduced  the  mor- 
tality from  17  to  6  per  cent.     The  following  formula  was  used: 

Quinine  hydrochlorate i .  00  gm. 

Sodium  chloride o.  75  gm. 

Distilled  water ; 10. 00  c.c. 

This  solution  is  more  highly  concentrated  than  necessary 
and  I  would  recommend  a  i  per  cent,  solution.  The  technic 
employed  is  similar  to  that  used  in  the  intravenous  injection  of 
salvarsan. 

Hypodermoclysis. — Quinine  dissolved  in  normal  salt  solution 
given  by  hypodermoclysis  has  been  recommended.  From 
10  to  30  grains  of  the  bimuriate  are  dissolved  in  a  pint  of 
normal  salt  solution,  and  as  much  as  desired  is  injected  into 
the  loose  subcutaneous  tissue.  This  method  is  probably  not 
adapted  to  the  treatment  of  algid  malaria  on  account  of  the 
deficient  superficial  circulation. 

Rectal  Administration. — This  method, .  though  uncertain,  is 
of  value  where  quinine  cannot  be  retained  by  the  stomach, 
and  there  are  objections  to  the  intramuscular  injection, 
especially  in  children.  It  may  also  be  used  as  an  adjuvant 
to  the  intramuscular  or  intravenous  injection  in  pernicious 
cases.  A  soluble  salt  should  be  used,  preferably  the  bimuriate. 
The  water  should  be  about  the  temperature  of  the  body, 
and  should  not  exceed  a  few  ounces  in  quantity.  Two  or  three 
times  as  much  quinine  should  be  given  by  the  rectum  as  by 
the  mouth,  and  the  injection  should  be  made  high  into  the 
bowel.  Ten  or  fifteen  drops  of  tincture  of  opium  should  be  added 
to  prevent  tenesmus  and  aid  retention.  Antipyrine  has  been 
recommended  by  some,  but  should  be  used  with  care  where 
there  is  depression.  A  cleansing  injection  should  be  given 
first  if  the  patient  is  conscious. 

Epidermic  Administration. — The  use  of  quinine  mixed  with 
fats  and  oils  and  rubbed  into  the  skin  is  not  to  be  relied  upon, 
since  little,  if  any,  quinine  is  absorbed  by  the  skin,  except  in 
young  children. 


2o8  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Time  of  Administration  and  Dose.^ — With  reference  to  the 
time  when  the  drug  is  given,  there  are  three  chief  modes  of 
giving  quinine: 

(i)  The  method  of  Torti,  a  single  dose  before  the  paroxysm; 
(2)  the  method  of  Sydenham,  a  single  dose  in  the  decKne  of  the 
paroxysm;  and  (3)  the  method  of  fractional  doses. 

The  first  two  methods  are  adapted  only  to  the  benign 
infections. 

The  efficacy  of  the  method  of  Torti  rests  upon  the  fact  that 
the  parasites  are  most  susceptible  to  the  action  of  quinine 
immediately  after  sporulation,  while  free,  before  having  entered 
the  red  cells.  It  presupposes  an  accurate  knowledge  of  the 
hour  at  which  the  next  paroxysm  will  occur,  based  obviously 
upon  a  definite  history  of  repeated  paroxysms,  a  temperature 
chart,  or  blood  examinations  sufi&ciently  accurate  to  deter- 
mine not  only  the  type  of  the  organism,  but  its  exact  stage. 
It  is  evident  that  in  private  practice,  in  the  patient  seen  in  the 
first  access,  the  prediction  of  the  next  paroxysm  must  usually 
depend  upon  the  results  of  the  examination  of  the  blood,  and 
that  this  must  be  repeated  if  the  stage  is  not  recognized  at 
the  first  examination.  Unless  this  can  be  done  quinine  should 
not  be  administered  in  this  way,  for,  even  if  the  type  of  malaria 
present  is  known,  there  are  two  conditions  which  may  render 
the  single  dose  futile:  first,  anticipation  of  the  paroxysm; 
second,  a  multiple  infection.  Even  where  the  blood  is  care- 
fully examined,  it  may  happen  in  double  infections,  that  only 
one  group  can  be  detected  in  the  peripheral  blood. 

By  this  method,  also  known  as  the  Roman  method,  the  qui- 
nine is  given  in  a  single  dose  of  about  1 5  grains  from  four  to  six 
hours  before  the  next  succeeding  paroxysm.  This  paroxysm 
is  not  prevented;  in  fact,  it  may  be  entirely  unmodified;  but 
such  a  dose,  properly  timed,  usually  secures  apyrexia  sub- 
sequently for  several  days. 

.  In  double  tertian  infections  a  single  dose  given  in  this  way 
may  change  the  quotidian  paroxysms  into  tertian,  and  if 
repeated,  in  multiple  tertian  and  quartan  infections,  con- 
stitutes a  sort  of  fractional  sterilization  of  the  blood. 

The  method  of  Sydenham,  the  English  method,  consists  of  a 


MALARIA  209 

single  dose,  averaging  15  grains,  given  in  the  sweating  stage 
of  the  decline  of  the  paroxysm.  This  dose  usually  prevents 
succeeding  paroxysms;  if  one  should  occur  it  is  usually  abortive. 

This  method  requires  less  knowledge  of  the  exact  nature  of 
the  infection  and  of  the  stage  of  development  than  the  former 
method;  hence  it  may  be  more  effectively  applied  by  the  busy 
practitioner.  What  experience  I  have  had  with  it  has  been 
satisfactory. 

The  third  method,  that  of  small  doses  at  frequent  intervals, 
has  numerous  advantages  over  the  one-dose  methods. 

1.  Quinine  given  in  this  way  is  better  borne  by  the  digestive 
and  nervous  systems. 

2.  The  loss  of  one  dose  by  vomiting  or  failure  of  absorption 
is  not  of  so  much  importance. 

3.  The  method  is  adapted  to  tertian,  quartan,  or  estivo- 
autumnal  infections;  this  is  important,  for  sometimes  these 
cannot  be  differentiated  clinically. 

4.  It  is  adapted  especially  to  estivo-autumnal  infections 
where  sporulation  is  not  so  nearly  synchronous. 

5.  The  time  of  administration  is  not  dependent  on  parasitic 
findings  or  definite  stages,  both  of  which  may  be  obscure  where 
the  patient  has  previously  taken  quinine. 

6.  An  experience  in  many  hundreds  of  cases  has  proved  its 
value. 

T  give  quinine  in  this  way  almost  exclusively.  The  average 
dose  is  a  grain  an  hour,  given  usually  2  grains  every  two  hours, 
3  grains  every  three  hours,  or  4  grains  every  four  hours,  day  and 
night.  It  is  especially  important  that  the  drug  be  given  uring 
the  night,  since  thus  only  may  the  blood  be  charged  during  the 
day,  when  sporulation  usually  occurs. 

Cinchonism  is  no  guide  to  the  quantity  to  be  given;  it  is  not 
the  patient  toward  which  the  quinine  is  directed,  but  the 
parasite. 

The  specific  should  not  be  discontinued  as  soon  as  the 
temperature  is  normal,  but  should  be  kept  up  for  at  least  two 
days  longer  in  the  quantity  employed  during  the  fever.  There- 
after about  15  grains  on  two  successive  days  of  each  week 
should  be  given  for  at  least  two  or  three  months  to  prevent 


2IO  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

relapse,  even  though  the  patient  leave  the  malarial  locality. 
A  few  days'  treatment  with  quinine  no  more  cures  malaria  than 
does  a  few  weeks'  rubbing  with  mercury  cure  syphilis. 

Hygienic  and  Symptomatic  Treatment. — Rest  is  important 
in  the  treatment  of  malaria  not  only  during  the  stage  of  active 
symptoms,  but  during  convalescence.  Exercise  may  counter- 
act the  benefits  of  quinine;  it  is  not  uncommon  to  see  cases 
yield  after  confinement  to  bed  which  had  previously  resisted 
quinine.  A  relapse  may  be  provoked  by  a  too  early  resump- 
tion of  duty.  Rest  is  especially  important  in  the  treatment  of 
estivo-autumnal  infections. 

Buttermilk  is  one  of  the  most  acceptable  and  easily  retained 
articles  of  diet.  Sweet  milk,  meat  broths,  vegetable  soups, 
fruit  juices  with  egg  albumin,  soft  boiled  eggs,  and  toast  are 
usually  allowable.  Where  there  is  much  gastric  disturbance 
food  had  better  be  withheld  temporarily. 

The  room  and  bed  should  be  screened;  in  this  way  only  can 
other  members  of  the  household  be  satisfactorily  protected. 
The  room  should  be  thoroughly  ventilated  and  the  patient 
protected  from  draughts. 

It  is  customary  to  begin  the  medical  treatment  with  a  purge. 
Calomel  is  the  drug  most  easily  administered  and  retained. 
The  drug  need  not  exceed  5  or  6  grains,  and  should  be  followed 
by  a  saline.  The  quinine  should  not  be  delayed  for  the  action 
of  the  purgative.  Calomel  has  been  frightfully  abused  in 
most  malarial  countries.  It  was  formerly  the  universal  prac- 
tice to  give  the  drug  until  the  gums  were  "touched"  and  the 
teeth  irreparably  damaged.  It  was  more  the  abuse  of  calomel 
than  of  any  other  drug  that  led  Oliver  Wendell  Holmes  to  declare 
that,  excepting  a  few  drugs,  "if  the  whole  materia  medica,  as 
now  used,  could  be  sunk  to  the  bottom  of  the  sea  it  would  be 
all  the  better  for  mankind  and  all  the  worse  for  the  fishes." 

During  the  cold  stage  blankets,  hot  drinks,  and  the  external 
applications  to  the  head,  tepid  sponging,  and  cold  rectal  in- 
jections may  be  used.  The  coal-tar  antipyretics  are  not  often 
indicated.     Cold  drinks  may  be  given. 

For  the  headache  cold  applications,  codeine,  and  acetanilid, 
or  chloral  and  bromide  of  soda  are   useful,  and   if  the  pain 


demands  it,  morphine  need  not  be  withheld.  If  nervousness 
is  marked  the  monobromated  camphor  should  be  administered 
with  the  quinine  in  capsules,  or  the  bromide  of  soda,  in  solution, 
with  each  dose  of  the  specific. 

For  vomiting,  if  intense  and  not  reheved  by  the  apphcation 
of  a  mustard  plaster  to  the  epigastrium,  morphine  should  be 
employed  subcutaneously. 

Chronic  Malaria. — In  the  treatment  of  chronic  malaria 
two  parasitic  cycles  have  to  be  combated,  the  schizogonic  and 
the  parthenogenetic.  The  treatment  of  the  asexual  cycle 
of  parasitic  evolution  in  chronic  malaria  is  that  of  acute 
malaria. 

The  tendency  to  relapse  at  multiples  of  approximately  seven 
days  has  long  been  recognized,  these  periods  being  known  as 
the  septenary  periods.  It  is  now  known  that  these  relapses 
depend  upon  the  sporulation  of  the  parthenogametes,  a  cycle 
difficult  to  interrupt  except  during  the  stage  of  free  spores. 

After  successfully  meeting  the  active  symptoms  by  quinine, 
administered  as  above  outhned,  the  prevention  of  a  relapse  is 
to  be  accomplished  by  giving  15  grains  of  quinine  every  sixth 
and  seventh  days  for  a  period  of  not  less  than  three  months. 
The  administration  of  a  valuable  salt  of  quinine  in  this  manner 
has  rarely  failed,  in  my  experience,  to  cure  the  most  obstinate 
case  of  chronic  malaria.  The  quinine  is  usually  given  in  3- 
grain  doses  every  three  hours  until  five  are  taken. 

The  hygienic  treatment  is  even  of  greater  importance  in  the 
management  of  chronic  malaria  than  in  acute.  Many  second- 
ary factors  may  arouse  latent  malaria,  and  these,  which  have 
been  mentioned  in  the  section  on  Etiology,  should  be  assidu- 
ously avoided.     A  change  of  climate  is  advisable. 

Cachexia. — Nothing  is  more  discouraging  to  the  physician 
than  the  treatment  of  cachectics  in  whom  the  poor  hygienic 
conditions  cannot  be  corrected,  which  is  not  rarely  the  case. 
The  two  chief  principles  involved  in  the  treatment  of  cachexia 
are,  first,  the  prevention  of  active  outbreaks  of  malaria,  and, 
second,  the  improvement  of  the  general  condition  of  the  patient 
by  appropriate  hygiene. 

Quinine  is  most  effectively  given  upon  two  successive  days 


212  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

in  each  week  as  described.  This  alone,  however,  will  rarely 
effect  a  cure  except  in  the  mildest  cases. 

Where  it  is  practicable  a  complete  change  of  climate  should 
be  advised.  Without  this  very  little  can  be  accomplished  for 
cases  of  severe  degree.  A  wholesome,  nutritious,  and  digestible 
diet  should  be  prescribed.  The  digestion  is  often  impaired 
and  stomachic  tonics  may  be  indicated.  Exposure  to  in- 
clement weather  must  be  avoided  on  account  of  the  dangers  of 
pneumonia.  Occupations  which  subject  the  cachectic  to  vio- 
lent exertion  or  to  bodily  harm  should  be  interdicted  for  fear 
of  rupture  of  the  spleen.  Regular  hours  must  be  kept  and 
constipation  overcome. 

Of  drugs  other  than  quinine,  arsenic  has  the  best  reputation. 
It  should  be  given  in  rather  large  doses  of  the  arsenious  acid 
or  Fowler's  or  Donovan's  solutions.  Atoxyl  has  recently 
been  introduced  into  the  treatment  of  malarial  cachexia. 
It  is  employed  hypodermically,  }-^  grain  being  a  moderate 
dose.  My  limited  experience  with  this  method  has  been  rather 
favorable  than  otherwise.  The  possibility  of  amaurosis  as  a 
toxic  result  of  atoxyl  should  be  borne  in  mind.  Cacodylate  of 
soda  has  given  me  good  results. 

Iron  is  nearly  always  indicated;  the  organic  preparations  of 
iron  and  manganese  are  usually  well  borne  by  the  stomach. 

Counter-irritation  over  the  splenic  area  may  aid  in  the  re- 
duction of  the  enlarged  spleen.  The  best  agent  is  the  ointment 
of  the  red  iodide  of  mercury.  A  piece  the  size  of  a  pea  or 
larger  should  be  thoroughly  rubbed  in,  the  splenic  region  being 
bared  to  the  sun's  rays  or  to  the  heat  of  a  fire.  This  should  be 
repeated  daily  until  the  skin  becomes  so  irritated  as  to  make 
friction  painful,  when  it  should  be  discontinued,  to  be  resumed 
again  when  the  condition  of  the  skin  will  permit.  Iodine,  tur- 
pentine, mustard,  firing  with  the  actual  cautery,  and  other 
counter-irritants  have  been  recommended. 

While  the  X-rays  have  a  destructive  eft'ect  upon  certain 
protozoa,  they  do  not  appear  to  have  such  action  upon  the 
parasites  of  malaria  within  the  circulation. 

Splenectomy  may  be  performed  in  very  anemic  patients  with 
large,  painful  spleens,r  especially  if  freely  movable,  in  whom  a 


MALARIA  213 

change  of  climate  is  impossible  and  therapeutic  measures 
have  failed.  I  had  the  opportunity  of  treating  an  obstinate 
case  of  estivo-autumnal  malaria  in  an  adult  female  who  had 
had,  several  years  previously,  the  spleen  removed  on  account 
of  malarial  cachexia.  Hemoglobin  percentage  was  only  slightly 
affected  by  the  attack,  and  convalescence  was  rapid. 

Treatment  of  Malaria  in  Children. — In  the  treatment  of 
malaria  in  children  it  is  my  practice  to  administer  the  quinine 
at  short  intervals,  every  two  or  three  hours. 

While  children  bear  quinine  in  relatively  larger  doses  than 
adults,  the  size  of  the  dose  should  be  regulated  by  the  severity 
of  the  attack  and  the  age  of  the  patient.  In  average  cases 
children  from  one-half  to  two  years  of  age  may  be  given  from 
^'2  to  I  grain  of  quinine  every  three  hours;  from  three  to  five 
years,  from  i  to  2  grains;  and  from  six  to  ten  years,  from  2  to 
23^^  grains.  These  quantities  may  be  increased  in  severe 
attacks. 

The  drug  is  ordinarily  given  by  the  mouth.  Where  capsules 
cannot  be  used,  recourse  must  be  had  to  a  tasteless  prepara- 
tion or  to  a  disguising  vehicle.  Euquinine  and  the  tannate  of 
quinine  are  the  best  of  the  tasteless  preparations.  The  former 
must  be  given  in  slightly  larger  doses,  the  latter  up  to  double 
the  doses  indicated  above.  The  most  efficient  liquid  for 
disguising  the  taste  of  the  sulphate  of  quinine  is  the  syrup  of 
yerba  santa,  at  least  i  dram  of  which  should  be  given  for  each 
2  grains  of  the  quinine.  In  cases  with  pernicious  symptoms 
the  drug  should,  of  course,  be  injected  intramuscularly.  Rectal 
administration  of  a  solution  or  suppository  may  be  employed 
to  supplement  other  modes.  The  buttocks  should  be  pressed 
together  for  half  an  hour  after  insertion  to  aid  retention. 

Calomel,  mercury  with  chalk,  and  castor  oil  are  efficient 
purgatives  in  the  treatment  of  malaria  in  children. 

Treatment  of  Complications. — When  malaria  is  complicated 
with  other  diseases  each  should  receive  appropriate  treatment, 
the  malaria  should  be  promptly  treated  as  under  ordinary 
circumstances.  Only  a  few  complications  need  special 
consideration. 

For  rupture  of  the  spleen  immediate  laparotomy  should  be 


214  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

performed.  With  early  operation  over  half  recover;  without 
operation  the  mortahty  is  nearly  loo  per  cent. 

Abscess  of  the  spleen  is  a  surgical  condition.  The  choice 
of  operation  between  splenectomy  and  splenotomy  must  be 
based  upon  individual  conditions. 

In  the  treatment  of  quinine  amaurosis  the  quinine  must,  of 
course,  be  discontinued.  Nitrite  of  amyl  and  nitroglycerine, 
with  tonics,  are  recommended. 

Substitutes  for  Quinine. — In  the  treatment  of  malaria  there 
is  no  drug  that  can  compare  in  efficacy  to  the  salts  of  quinine ; 
nevertheless,  in  rare  instances  it  becomes  necessary  on  account 
of  idiosyncrasy  to  resort  to  the  use  of  other  remedial  agents. 

While  the  newer  preparations  of  quinine,  euquinine,  salo- 
quinine,  aristochin,  etc.,  are  purported  to  be  free  from  the 
toxic  properties  of  the  official  salts,  I  have  seen  one  case  in 
which  euquinine  caused  distressing  dyspnea,  and  another  case 
in  which  this  preparation  caused  violent  urticaria.  Euquinine 
is  probably  the  most  valuable  of  these  preparations. 

The  alkaloids  of  cinchona,  other  than  quinine,  are  now  but 
rarely  employed,  and  opinions  vary  widely  as  to  their  merits. 
Cinchonidine  is  probably  the  most  useful  of  these  alkaloids. 
It  must  be  given  in  doses  about  twice  as  large  as  of  quinine. 
These  alkaloids,  especially  cinchonine  and  quinidine,  are 
more  toxic  than  quinine,  producing  nervous  and  gastric  dis- 
order and,  in  toxic  doses,  convulsions. 

Good  results  have  been  obtained  with  Warburg's  tincture. 
It  is  claimed  that  quinine  may  be  given  in  this  form  when  not 
tolerated  otherwise.  The  liquid  contains,  among  its  many 
ingredients,  about  lo  grains  of  quinine  to  the  ounce,  and  the 
dose  is  1 2  ounce  repeated  in  two  to  four  hours.  It  is  probable 
that  as  good  effects  can  be  obtained  by  quinine  alone  in  solu- 
tion as  with  this  unpalatable  and  unscientific  conglomeration 
of  "quinine  concealed  in  a  farrago  of  inert  substances  for  pur- 
poses of  mystification."  Its  composition  was  for  a  long  time  a 
secret. 

Methylene-blue  was  introduced  into  the  treatment  of  malaria 
by  Guttmann  and  Ehrlich^^"  in  1891. 

In  my  experience  this  is  the  best  substitute  for  the  derivatives 


MALARIA  215 

of  Peruvian  bark.  While  it  does  not  compare  favorably  with 
quinine,  requiring  a  longer  time  to  effect  a  cure  and  failing  al- 
together in  not  a  few  instances,  it  seems  to  possess  some  specific 
action  upon  the  parasites  of  malaria,  and  is  the  most  valuable 
drug  where  the  cinchona  preparations  are  absolutely  contra- 
indicated. 

Only  the  purest  preparation  should  be  employed  for  medicinal 
purposes,  otherwise  untoward  results  may  follow. 

The  dose  is  from  1)2  to  3  grains  given  every  three  hours 
until  from  yj^  to  15  grains  have  been  given  in  twenty-four 
hours.  The  drug  may  be  continued  in  this  manner  for  several 
days. 

Untoward  symptoms  caused  by  the  administration  of  methy- 
lene-blue  are  headache,  nausea,  vomiting,  diarrhea,  strangury, 
and  albuminuria.  These  effects  are  less  apt  to  supervene  when 
a  pure  article  is  given.  The  patient  should  always  be  fore- 
warned of  the  blue  color  imparted  to  the  urine  and  feces. 

After  its  introduction  in  1842  by  Boudin  arsenic  enjoyed, 
until  recently,  considerable  reputation  in  the  treatment  of 
malaria.  The  old  school  of  physicians  claimed  results  but 
little  inferior  to  those  with  quinine.  More  recent  observations 
show  that  if  this  agent  has  any  value  in  the  treatment  of 
malaria  it  is  in  the  chronic  form.  Whether  its  good  efl'ects  here 
are  chiefly  upon  the  anemia  and  as  a  general  tonic  or  whether 
it  has  some  action  upon  the  parthenogenetic  cycle  is  not  deter- 
mined. Fowler's  solution  and  the  arsenious  acid  are  the  prepa- 
rations usually  employed.  The  dose  at  the  beginning  should 
be  small  and  gradually  increased.  Upon  the  appearance  of 
puffiness  of  the  eyelids,  colicky  pains  in  the  abdomen,  and 
diarrhea  the  dose  should  be  diminished  or  its  use  temporarily 
discontinued.  The  arsenious  acid  may  well  be  combined  with 
iron,  quinine,  and  strychnine  in  the  treatment  of  chronic  malaria. 

Two  recent  preparations  of  arsenic,  arthenal  or  disodic 
methylarsenate,  and  sodium  cacodylate  have  been  vaunted  as 
antimalarials.  They  are  rich  in  arsenic,  but  less  toxic.  They 
are  usually  given  hypodermically  in  doses  of  from  fg  to  1,1 2 
grains  daily.  I  have  had  good  results  with  the  latter  prepara- 
tion, especially  in  chronic  malaria. 


2l6  ENDEMIC   DISEASES    OF   THE    SOUTHERN    STATES 

The  benefits  derived  from  atoxyl  in  the  treatment  of  try- 
panosomiasis led  to  an  investigation  of  its  merits  in  malaria. 
Chemically,  atoxyl  is  sodium  aminophenyl  arsenate,  containing 
about  25  per  cent,  of  arsenic  and  soluble  at  2o°C.  in  4.3  parts 
of  water.  The  usual  dose  is  from  1-3  to  i  grain,  given  every  day 
or  every  other  day,  usually  hypodermically.  It  cannot  be 
regarded  as  a  substitute  for  quinine. 

There  is  no  doubt  but  that  salvarsan  cures  some  cases  of 
malaria  where  all  other  means  fail.  Such  cases  are  doubtless 
those  in  which  "quinine-fast"  organisms  are  present.  The 
drug  should  be  administered  by  the  usual  technic  in  ordinary 
dosage  at  weekly  intervals. 

Opium  is  not  only  effective  agairjst  certain  symptoms  of 
malaria,  but  it  has  been  shown  to  possess  antiperiodic  virtue. 
This  is,  in  all  probability,  due  to  the  narcotine  contained. 
For  this  reason  opium,  in  the  form  of  the  powder,  Dover's 
powder,  laudanum,  or  paregoric,  is  more  effective  than  mor- 
phine. The  immunity  of  opium  smokers  to  malaria  has  been 
remarked  upon  by  a  number  of  tropic  physicians. 

A  large  number  of  other  substances  have  been  recommended 
as  substitutes  for  quinine.  The  chief  of  these  are  phenocoll, 
eucalyptus,  salicin,  salicylic  acid,  sodium  hyposulphite,  etc. 
Their  antimalarial  value,  if  indeed  they  possess  any,  is  so  slight 
as  to  render  a  detailed  consideration  not  worth  the  while. 

The  serum  treatment  of  malaria  has  not  yet  reached  the  stage 
of  practical  utility. 

Recently  Carpenter^''^  claims  remarkable  success  in  the 
treatment  of  malaria  with  powdered  splenic  extract  in  the  dose 
of  5  grains  every  two  to  four  hours,  preferably  in  capsules. 
He  states  that  it  is  equally  as  reliable  a  remedy  as  quinine. 

The  Treatment  of  Pernicious  Malaria. — There  are  certain 
cases,  apparently  on  the  borderline  between  benign  malaria  and 
pernicious  malaria  of  the  cerebral  type,  which  may  cause  hesita- 
tion as  to  the  mode  of  administration.  In  these  cases,  usually 
in  children,  the  patient,  though  stupefied,  or  even  semicomatose, 
can  be  aroused  and  made  to  swallow  and  usually  retain  the 
medicine.  In  such  cases,  if  the  patient  can  be  watched,  the 
quinine  may  be  given  in  solution  by  the  mouth.     If  vomited 


MALARIA 


217 


or  if  the  symptoms  do  not  rapidly  improve,  the  drug  in  dilute 
solution  should  be  injected  intramuscularly.  Where  the  in- 
jection mode  is  chosen  it  is  advisable  to  supplement  this  with 
oral  administration  of  the  solution  where  it  can  be  swallowed, 
and  even  the  rectum  may  be  employed  also. 

As  previously  stated,  quinine  for  intramuscular  injection 
should  be  in  dilute  solution;  15  grains  to  2}-^  drams  of  water  is 
a  suitable  proportion.  The  gluteal  region,  above  the  ischial 
tuberosities,  is  the  best  site  for  injection.  In  pernicious 
cases  about  15  grains  is  the  quantity  to  be  used  at  first  in- 
jection. Subsequent  doses  may  be  from  5  to  10  grains  injected 
every  six  or  eight  hours  as  needed.  The  technic  of  such 
injections  has  already  been  given. 

Just  as  antisyphilitics  may  cause  the  gumma  to  melt  rapidly 
but  are  powerless  to  restore  the  tissue  they  have  destroyed, 
so  quinine  has  its  limitations  in  the  therapeutics  of  malaria. 
It  should  be  borne  in  mind  that  in  its  relation  to  the  parasites 
quinine  is  a  toxin,  but  not  an  antitoxin.  It  is  impossible  that 
where  the  parasites  are  accumulated  to  the  extent  of  throm- 
bosis the  quinine  in  solution  in  the  blood  does  not  reach  them 
in  toxic  quantities,  and  where  perivascular  exu,dation,  hemor- 
rhage, and  necrosis  have  resulted  from  these  thrombi  the 
annihilation  of  the  parasites  avails  nothing.  This  is  corrob- 
orated by  those  cases  ending  fatally,  notwithstanding  a  rapid 
disappearance  of  the  parasites,  and  in  which  post-mortem 
these  secondary  changes  are  found.  All  that  can  be  expected 
of  quinine  is  to  destroy  the  parasites,  and  this  it  may  fail  to 
accomplish  from  not  being  absorbed  or  not  being  present  in 
the  blood  in  sufHcient  quantities  or  at  the  time  when  the 
parasites  are  most  susceptible  to  its  action  or  on  account  of 
thrombotic  occlusions  it  may  not  gain  access  to  the  parasites 
causing  the  symptoms.  Quinine  is  probably  a  true  specific 
in  those  cases  of  pernicious  malaria  only  in  which,  in  the 
absence  of  irreparable  changes  due  to  toxins  or  to  thrombi,  the 
prompt  destruction  of  the  parasites  would  be  attended  by  an 
almost  simultaneous  cessation  of  symptoms. 

Other  than  the  specific  treatment  there  are  important 
symptomatic  indications  to  be  met. 


2l8  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

In  cases  with  high  temperature  and  hot  dry  skin,  cooling 
baths  should  be  used.  For  heart  depression  strychnine  or 
digitalis  are  useful. 

In  the  cerebral  types  the  ice-bag  to  the  head  is  called  for 
and  an  active  cathartic  should  be  given  if  possible.  Where  this 
cannot  be  swallowed,  a  drop  of  croton  oil  on  the  back  of  the 
tongue  may  be  tried.  If  delirium  is  marked,  a  solution  of 
chloral  and  the  bromides  should  be  given  by  the  rectum. 
Where  there  are  convulsions,  chloral  and  bromides  by  the 
rectum,  morphine  hypodermically,  or  even  inhalations  of 
chloroform  may  be  necessary.  Bell  employed  lumbar  puncture 
in  a  case  of  malarial  coma  to  relieve  the  increase  in  the  cere- 
brospinal fluid  which  usually  exists  in  these  cases,  but  the 
result  was  disappointing. 

In  algid  attacks  for  the  relief  of  cold  surface  and  dyspnea, 
especially  if  choleraic  symptoms  are  present,  nothing  is  so 
suitable  as  a  combination  of  morphine  and  atropine.  The 
heart  usually  requires  stimulation  by  strychnine  and  digitalis. 
Hypodermics  of  ether  may  be  necessary.  If  dysenteric  symp- 
toms arise  they  should  be  treated  with  opium  and  bismuth, 
together  with  saline  irrigations. 

If  complications  appear  they  should  receive  appropriate 
treatment. 

During  convalescence  a  tonic  of  arsenic,  strychnine,  iron, 
and  quinine  is  usually  indicated.  In  cases  where  it  is  feasible, 
a  change  of  climate  should  be  ordered  until  recovery  is  thor- 
oughly established. 


BLACKWATER  FEVER 


CHAPTER  IX 
INTRODUCTION 

Blackwater  fever  is  known  by  many  names,  some  of  which 
are  mere  localisms.  Among  the  more  general  synonyms 
are:  malarial  hematuria,  hemoglobinuric  fever,  swamp  fever, 
bilious  hematuric  fever,  and  melanuric  fever. 

History. — It  is  probably  unique  in  historic  pathology  that  a 
complex  of  symptoms  so  striking  as  hemoglobinuric  fever 
should  have  such  an  obscure  history.  As  this  obscurity  is 
intimately  associated  with  the  etiology  and  symptomatology 
of  the  condition  an  investigation  of  some  of  the  factors  in  its 
history  is  not  without  interest.  After  a  short  statement  of 
the  history  of  hemoglobinuric  fever  we  will  briefly  consider  how 
far  it  has  been  influenced  by  (i)  its  confusion  with  bilious 
remittent  fever  and  yellow  fever,  (2)  the  introduction  of 
cinchona  bark  and  its  alkaloids  into  the  treatment  of  malaria, 
and  (3)  the  advent  of  Europeans  into  endemic  regions. 

In  the  years  from  1850  to  1853  blackwater  fever  was  described 
by  Lebeau,  DauUe,  and  Leroy  de  Mericourt,  physicians  of  the 
French  navy,  who  observed  it  in  Madagascar,  and  especially 
on  the  Island  of  Nossi  Be,  off  the  northwest  coast  of  the  former 
island.  They  named  the  condition  icteric  pernicious  fever. 
In  1861  cases  observed  in  the  Antilles,  Guiana,  and  Senegal 
were  described  by  Dutrouleau  as  hematuric  bilious  fever. 
In  the  early  sixties  Barthelemy-Benoit  also  described  hematuric 
bilious  fever,  and  in  1874  appeared  the  monograph  of  Berenger- 
Feraud  on  melanuric  bilious  fever.  This  writer  states  that 
the  disease  has  existed  in  Goree  since  1845,  ^^'^  ^^  St.  Louis, 
in  Senegal,  according  to  the  hospital  records  of  that  city,  at 
least  since  1820,  shortly  after  the  settling  of  the  Europeans 
there.     The   first   twenty-three   settlers    at    Gabun,   in   1843, 


2  20  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

were  attacked  with  blackwater  fever  and  almost  all  of  them 
died.     A  great  increase  in  frequency  has  occurred  since  1850. 

Crosse'  believes  his  own  case,  in  1888,  to  be  the  first  on 
record  in  the  Niger  Territories,  though  he  states  that  the 
disease  was  said  by  old  coasters  to  have  existed  in  the  Niger 
Delta  since  1882.  F.  Plehn-  does  not  believe  the  disease  to 
be  of  recent  introduction  into  West  Africa,  but  attributes  its 
comparatively  late  recognition  to  two  facts — first,  that  the 
susceptible  population,  who  formerly  lived  as  traders  on 
anchored  hulks,  began  to  take  up  their  abode  on  the  shore; 
second,  that  the  disease  was  formerly  confounded  with  yellow 
fever.  It  has  been  shown  in  Senegambia  since  1885,'  and  in 
the  Dutch  East  Indies  since  the  Atjeh  War,  1874-78.*  Cal- 
mette  saw  a  number  of  cases  in  Gabun  in  1886-87,  and  Fluit, 
in  San  Juan  del  Sur,  has  seen  numerous  cases  since  1850.^ 
The  condition  was  not  described  in  India  until  1855,  and  Sam- 
bon'^  regards  this  as  conclusive  of  its  recent  introduction,  as 
"it  would  be  absurd  to  think  that  it  could  have  escaped  the 
attention  of  such  men  as  Annesley,  Chevers,  Carter,  Martin, 
Fayrer,  Morehead,  and  Maclean  had  they  met  with  it." 

Dr.  Elliotson,^  in  1832,  mentioned  a  case  of  ague  accompanied 
by  a  discharge  of  bloody  urine  during  the  cold  stage. 

Todd,^  in  1849,  asserted  that  "a  state  of  general  cachexia, 
such  as  often  occurs  in  scurvy,  may  bring  on  hematuria,  or 
such  as  results  from  an  aguish  state  brought  on  by  the  malaria 
of  marshy  districts." 

In  the  United  States  hemoglobinuric  fever  was  first  de- 
scribed by  Dr.  J.  C.  Cummings,^  of  Monroe,  Louisiana,  in 
1859.  He  reported  six  cases,  and  refers  to  numerous  cases 
during  the  previous  season.  Faget*  treated  the  disease  as 
early  as  1859,  ^.nd  states  that  the  cases  with  hematuria  and 
hematemesis  had  frequently  been  seen  in  New  Orleans  and 
been  mistaken  for  yellow  fever.  Inasmuch  as  Faget  con- 
sidered hematemesis  a  common  symptom  of  hemoglobinuric 
fever,  it  is  possible  that  he  himself  confounded  the  two  diseases 
in  some  instances.  In  1867  Dr.  T.  C.  Osborn'  of  Greensboro, 
Ala.,  observed  ten  cases,  five  of  which  ended  fatally,  some 
with  anuria  and  uremia.     All  the  patients  had  been  repeatedly 


BLACK  WATER    FEVER  221 

attacked  with  malaria.  A  few  months  later  his  son,  Dr.  J.  D. 
Osborn,^"  read  a  paper  before  the  Greensboro  Medical  Society 
from  which  it  is  evident  that  the  disease  was  becoming  more 
prevalent,  and  that  the  country  people  were  regarding  it  as 
yellow  fever.  Dr.  H.  C.  Ghent^^  of  Port  Sullivan,  Texas, 
in  1866  reported  hemoglobinuric  fever  endemic  in  parts  of 
Texas.  In  March,  1869,  Dr.  R.  F.  Michel,  of  Montgomery, 
Ala.,  read  a  paper  before  the  Medical  Association  of  the  State 
of  Alabama  in  which  he  spoke  of  the  disease  as  "a  malignant 
malarial  fever,  following  repeated  attacks  of  intermittent, 
characterized  by  intense  nausea  and  vomiting,  very  rapid 
and  complete  jaundiced  condition  of  the  surface  as  well  as 
most  of  the  internal  organs  of  the  body,  an  impacted  gall- 
bladder, and  hemorrhages  from  the  kidneys.  These  phenomena 
presented  themselves  in  an  almost  uninterrupted  Hnk,  attended 
by  remissions  and  exacerbations.  It  is  a  fever  peculiar  to  the 
United  States."  He  recorded  the  morbid  anatomy  in  one  of 
his  fatal  cases.  In  Arkansas  hemoglobinuric  fever  was  first 
recorded  by  Dr.  E.  R.  Duvall,  of  Fort  Smith,  in  a  paper  read 
before  the  State  Society  in  1871.  He  beheved  the  case  he 
recorded  to  be  the  first  to  occur  in  the  state.  This  paper  is 
said  to  be  a  model  of  accurate  clinic  observation.  In  1880 
Dr.  G.  B.  Malone,  in  Monroe  County,  Arkansas,  reported  155 
cases  met  in  his  practice.  The  affection  was  first  reported  in 
Georgia  by  Dr.  W.  A.  Greene,  of  Americus,  in  1872,  and  in 
North  Carolina  by  Dr.  Norcom,  of  Edenton,  in  1874.  Norcom 
asserts  that  the  disease  did  not,  as  some  claimed,  make  its 
first  appearance  a  few  years  ago,  but  that  it  had  long  been 
recognized.  Dr.  McDaniel,^  of  Camden,  Alabama,  described 
hemoglobinuric  fever  in  1874,  and  says,  "In  calling  up  my  own 
reminiscences,  I  am  sure  that  I  have  occasionally,  ever  since  my 
boyhood,  seen  isolated  cases  of  what  was  considered  intense 
bilious  fever  with  the  surfaces  and  under  tissues  stained 
deeply  yellow  and  with  the  urine  deep  red.  They  were  nearly 
all  fatal,  and  were  called  in  older  phrase  'bilious  congestive,' 
and  in  more  recent  'pernicious  bilious.'  I  have  also,  but  more 
rarely,  known  groups  of  similar  cases  associated,  say  three  or 
four  cases  occurring  on  the  same  premises  or  in  the  same 


222  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

family,  about  the  same  time.  All  such  cases,  in  addition  to 
the  deep  so-called  bilious  color  and  the  red  urine,  had  jactita- 
tion, suspirous  breathing,  inordinate  thirst,  and  vomiting  of 
various  shaded  and  tinted  so-called  bilious  matters.  By 
diligently  inquiring  I  have  ascertained  that  very  many  old 
physicians,  some  of  whom  have  now  retired  from  practice, 
are  satisfied  that  they  have  observed  similar  cases,  sometimes 
singly  and  sometimes  in  groups." 

The  late  lamented  Dr.  A.  G.  Mabry,  in  a  report  of  a  case  of 
intermitting  icterode  hematuric  fever  made  to  this  association 
in  1870,  says,  "It  is  a  mistake  to  suppose  that  this  is  a  new 
form  of  disease.  More  than  twenty-five  years  ago  I  treated, 
in  the  vicinity  of  Selma,  cases  of  intermitting  fever  presenting 
in  a  marked  degree  all  the  symptoms  characteristic  of  these 
cases  at  the  present  day." 

The  acrimonious  dispute  of  the  earliest  writers  on  the  sub- 
ject of  what  constituted  the  coloring  matter  of  the  urine  is 
paralleled  only  by  that  occurring  later  concerning  quinine  in 
the  treatment.  While  Daulle  and  Berenger-Feraud  stoutly 
maintained  that  the  dark  color  was  due  to  the  presence  of 
bile  in  the  urine,  Dutrouleau,  Pellarin,  Barthelemy-Benoit, 
Antoniades,  and  Corre  ascribed  it  to  blood.  It  is  remarkable 
that  none  of  the  first  American  writers  attributed  the  color 
of  the  urine  to  bile,  but  considered  it  due  to  blood.  Corre 
(1881)  and  Karamitsas  (1882)  proved  that  the  process  was  a 
hemoglobinuria  instead  of  a  hematuria. 

The  credit  of  first  directing  attention  to  the  etiologic  relation 
between  quinine  and  hemoglobinuric  fever  is  generally  credited 
to  Tomaselli  who  pubhshed  his  first  observations  in  1874,  but 
this  is  an  error.  At  a  meeting  of  the  Greek  Medical  Society, 
Nov.  6,  1858,  Veretas^'  reported  that  the  majority  of  phy- 
sicians practising  in  the  marshy  regions  of  Greece  had  noticed 
hematuria  following  the  administration  of  quinine.  He  adds, 
"Among  these  observers  my  father  has  a  place,  having 
attentively  observed  this  action  of  the  medicament  not  only 
in  several  other  persons,  but  in  himself  also,  unfortunately,  as 
he  was  for  a  long  time  tormented  with  intermittent  fever  dur- 
ing his  long  residence  at  Vonitsa."     Konsola'-  is  said  to  have 


BLACKWATER    FEVER  223 

observed  similar  cases  in  1858.  During  this  year  also,  Anto- 
niades  published  an  article  on  "Hemorrhages  and  Particularly 
Hematuria  in  Intermittent  Fever,"  in  which  he  opposes  the 
theory  that  quinine  is  a  cause.  Other  Greek  physicians  whose 
observations  were  pubHshed  before  those  of  Tomaselli  are 
Papavassilou,  Rizopoulos,  and  Karamitsas. 

I.  The  close  relationship  between  malaria  and  blackwater 
fever  renders  it  easily  understood  why  the  latter  might  have 
been  confounded  with  bilious  remittent  fever.  Moreover,  the 
early  pyretologists  almost  completely  ignored  the  condition  of 
the  urine  in  fevers.  Hence,  in  a  clinical  scene,  preceded  by  or 
opened  with  ordinary  malarial  paroxysms  and  characterized 
by  dark  urine,  between  the  color  of  which  and  the  bilious 
urine  of  bilious  remittent  fever  there  are  all  degrees,  it  is  shght 
wonder  that  the  two  conditions  were  confounded. 

This  probably  occurred  chiefly  in  India  and  to  a  less  extent 
in  certain  portions  of  Africa  and  America.  One  is  struck, 
on  reading  accounts  of  the  Indian  fevers,  with  the  description 
of  the  intense  jaundice  of  the  skin  and  sclarae,  out  of  all  pro- 
portion to  this  symptom  in  the  bilious  remittent  fevers  of  the 
present  day.  In  fact,  some  of  these  descriptions — for  in- 
stance, Johnson's'^  of  his  first  case  in  India — lack  only  the 
mention  of  the  characteristic  urine,  about  which  the  author  is 
altogether  silent,  to  make  a  fairly  complete  case  of  hemoglo- 
binuric  fever.  Since  it  is  reasonably  certain  that  there  was  no 
yellow  fever  in  Minorca  during  the  period  of  Cleghorn's  sojourn 
in  the  island,  namely  from  1774  to  1749,  it  may  reasonably  be 
inferred  that  he  saw  cases  of  blackwater  fever. 

In  1804,  Alibert,  in  the  third  edition  of  his  work,  wrote:  "The 
state  of  the  urine  in  malignant  fevers  demands  great  atten- 
tion." Thus  a  diminution  of  that  excretion  and  its  assuming 
a  black  color  are  very  alarming  symptoms. 

The  fact  that  the  early  history  of  hemoglobinuric  fever 
opens  with  disputes  as  to  whether  the  coloring  matter  of  the  urine 
was  due  to  blood  or  to  bile  is  evidence  of  the  confusion  by 
some  observers  between  hemoglobinuric  fever  and  bilious 
remittent  fever,  since  formerly  bile  and  malaria  were  practically 
synonymous. 


2  24  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

It  has  been  mentioned  that  the  first  reliable  records  of  the 
existence  of  hemoglobinuric  fever  were,  according  to  Berenger- 
Feraud,  those  of  the  hospital  of  St.  Louis  in  Senegal,  where  It 
is  shown  to  have  existed  as  early  as  1820.  It  is  a  singular 
coincidence  that  this  city  afforded  in  1778,  the  first  epidemic 
of  yellow  fever  occurring  in  Africa.  ^^  Later  Plehn-  gave  as 
one  of  his  reasons  for  believing  that  hemoglobinuric  fever  was 
not  a  new  disease  in  West  Africa,  that  it  had  formerly  been 
mistaken  for  yellow  fever.  Besides  Senegal,  two  of  the  other 
regions  where  hemoglobinuric  fever  was  first  seen,  the  West 
Indies  and  Guiana,  were  yellow  fever  foci.  In  the  United 
States  we  have  the  early  statement  of  Dr.  J.  D.  Osborne  that 
the  condition  was  then  regarded  as  yellow  fever. 

The  similarity  of  the  symptoms  and  the  relative  immunity 
of  the  black  race  to  both  diseases  render  the  mistake  some- 
what excusable.  As  recently  as  1897  Below^®  maintained 
the  identity  of  yellow  fever  and  blackwater  fever. 

2.  Cinchona  bark  was  introduced  into  Europe  in  1640  by 
the  Countess  del  Cinchon,  wife  of  the  vice-regent  of  Peru,  in 
whose  honor  it  has  received  its  name.  The  efficacy  of  the  bark 
in  malaria  was  first  known  to  the  Indians  in  the  region  of 
Loxa,  in  the  southern  portion  of  Ecuador.  The  Corregidor 
of  Loxa,  hearing  of  the  severe  illness  of  the  countess  with 
tertian  fever  at  Lima,  in  1638,  advised  her  physician,  de  Vega, 
to  give  the  bark  a  trial,  which  effected  a  prompt  cure,  and  in 
those  days  was  regarded  as  nothing  short  of  miraculous. 

When  the  countess  returned  to  Spain  she  took  a  supply  of 
the  bark  with  her.  Here  it  seems  first  to  have  been  employed 
chiefly  by  the  Jesuits  who  introduced  it  into  Rome  in  1649. 
It  was  then  known  as  countess'  powder  or  Jesuits'  powder. 
Its  use  was  antagonized  by  other  religious  denominations  and 
by  the  medical  profession.  Bark  was  imported  into  England 
in  1 61 7  by  Sir  Robert  Talbot,  an  Enghsh  quack,  who  kept  the 
remedy  a  secret  and  sold  it  for  one  hundred  louis  d'or  per 
pound.  Louis  XIV,  who  was  attacked  with  a  rebellious  and 
severe  intermittent  in  the  year  1679,  was  cured  by  Talbot  with  a 
concentrated    vinous    tincture    of    the    bark,    purchased    and 


BLACKWATER    FEVER  22$ 

made  public  the  secret  remedy,  for  which  he  paid  £48,000 
and  a  life  annuity  of  £2,000. 

In  India  the  remedy  was  employed  by  Bogue'^  as  early  as 
1657.  In  these  times  in  Spanish-America,  where  the  bark  was 
indigenous,  extraordinary  methods  were  employed  to  prevent 
the  nature  of  the  drug  becoming  recognized.  But  during  the 
eighteenth  century  cinchona  bark  was  almost  universally 
known.  Lind  is  said  to  have  employed  in  Lower  Senegal, 
during  1765,  over  140  pounds  of  the  bark.  In  17 14,  Ramazzini^^ 
wrote  that  should  a  fever  patient  die  it  was  considered  a  crime 
not  to  have  employed  cinchona.  In  fact,  so  widespread  was 
the  use  of  large  doses  of  bark  that  Calmenero  (1647),  Casati 
(1661),  Daval  (1684),  Ramazzini  (1714),  and  others  wrote 
vehemently  against  the  abuse  of  the  drug. 

Pelletier  and  Caventou,  in  1820,  succeeded  in  isolating 
quinine  from  the  bark. 

The  institution  of  cinchona  plantations  in  Java  in  1854  and 
in  Ceylon  in  1859  caused  a  drop  in  the  price  of  quinine,  which 
had  formerly  sold  for  its  actual  weight  in  gold,  to  one-twentieth 
the  original  price. 

Marchiafava  and  Bignami^'  seek  to  explain  the  seeming 
late  appearance  of  hemoglobinuric  fever  by  the  use  of  quinine 
becoming  prevalent  at  the  time  when  the  disease  was  first 
described.  It  is  probable  that  this  factor  has  caused  an 
increase  in  certain  localities,  but  a  comparison  of  the  history 
of  the  disease  with  that  of  the  drug  shows  no  very  intimate 
chronologic  relations.  Further,  blackwater  fever  is  on  the 
decrease  in  some  regions  where  the  use  of  quinine  is  becoming 
more  general.  This  is  reported  to  be  the  case  in  German 
East  Africa  by  Meixner,^"  in  Cameroon  by  Ziemann,^"  in  Togo 
by  A.  Plehn,^^  and  by  Kohlbrugge*  in  the  Malay  Archipelago. 
The  large  number  of  cases  occurring  without  the  previous  use 
of  quinine  should  also  be  considered. 

3.  A  consideration  of  the  importance,  in  the  history  of 
hemoglobinuric  fever,  of  the  immigrations  of  Europeans  into 
regions  where  the  condition  is  endemic  involves  the  history 
of  the  tropics  and  subtropics.  This  factor  is  manifestly  an 
essential  in  countries  where  the  natives  are  nearly  immune, 
IS 


2  26  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

as  in  parts  of  Africa.  Historic  events,  which  were  probably 
potent  in  the  development  of  blackwater  fever,  were  the  dis- 
covery of  America,  the  Portuguese  discoveries  and  settlements 
on  the  coast  of  Africa,  the  African  slave  trade  and  the  later 
efforts  to  abolish  same,  the  advent  to  Africa  of  missionaries 
and  explorers,  especially  in  the  early  part  of  the  nineteenth 
century,  and  the  operations  of  the  East  India  Company. 

The  accession  of  Europeans  was  influential  ''n  the  history 
of  hemoglobinuria  fever  in  several  ways — by  the  increase  of 
susceptible  population,  by  the  importation  of  quinine,  and  by 
the  advent  of  physicians  competent  to  recognize  and  to  de- 
scribe the  disease. 

Geographic  Distribution. — In  North  America  hemoglo- 
binuric  fever  is  found  in  the  Southern  States,  especially  parts 
of  Texas,  Louisiana,  Arkansas,  Mississippi,  Tennessee,  Alabama, 
Georgia,  Florida,  North  Carolina,  South  Carolina,  and  Vir- 
ginia. It  is  prevalent  in  Central  America,  particularly  in 
Honduras,  Nicaragua,  and  Costa  Rica.  It  is  found  in  the 
Greater  Antilles,  but  appears  to  be  rare  in  Hayti.  In  the 
Lesser  Antilles  it  is  more  common  on  the  islands  of  Gaudeloupe 
and  Martinique.  Numerous  cases  have  been  reported  from 
Panama.  In  South  America  hemoglobinuria  fever  prevails 
more  notably  on  the  north  and  east  coasts,  in  Venezuela,  Guiana, 
and  Brazil,  at  least  as  far  south  as  Rio  de  Janeiro. 

It  is  rare  in  Italy,  but  rather  more  common  in  Sicily,  Sardinia, 
and  Greece.  Otto^^has  reported  an  autochthonous  case  from 
Krakau.  It  has  appeared  in  some  of  the  valleys  of  Spain,  and, 
according  to  Schoo,  was  formerly  observed  in  Holland. 

The  regions  in  India  in  which  hemoglobinuria  fever  is 
endemic  are  as  follows:  Between  the  Ganges  and  the  Himalayas 
in  Behar  Province;  between  the  Godavari  and  the  Mahandi 
Rivers  in  the  Madras  Presidency;  a  region  of  which  Nagpur  is 
the  center;  certain  localities  in  the  region  of  Bombay;  and  in 
Assam  and  in  Upper  Burmah.  It  is  found  in  Asia  Minor, 
Cyprus,  and  Syria  (being  common  in  Palestine),  the  Malay 
Peninsula,  Siam,  Cochin-China,  Tonking,  and  other  portions 
of  French  Indo-China,  and  in  Southern  China.  In  the  East 
Indies  it  appears  in  Sumatra,  Java,  Celebes,  and  more  commonly 


BLACK  WATER    FEVER  227 

in  New  Guinea  and  the  Bismarck  Archipelago.  It  has  been 
reported  from  Formosa,  but  is  comparatively  rare  in  the 
Philippines. 

Tropical  Africa  is  the  home  of  blackwater  fever.  Here 
between  the  parallels  of  i5°N.  and  i5°S.,  it  has  been  one  of  the 
deadliest  foes  to  civilization.  On  the  West  Coast  it  occurs 
from  Senegal  to  Damara  Land,  especially  in  Sierra  Leone, 
Gold  Coast,  Nigeria,  Cameroon,  and  the  Congo  Region.  On 
the  East  it  prevails  from  Somali  Land  to  Delago  Bay, 
particularly  in  British  and  German  East  Africa  and  the  Congo 
Free  State,  and  is  met  with  in  the  Bahr-el-Ghazal  region  and 
in  Sudan.  In  Algeria,  Laveran,^^  during  a  residence  of  five 
years,  did  not  observe  a  single  case  and  Brault^^  saw  only 
one.  However,  Coste^^  has  recently  published  his  observations 
of  25  cases  treated  during  1904-05  in  the  region  of  Arzew.  It 
rages  in  parts  of  Madagascar  and  Reunion,  and  is  known  in 
Mauritius  and  the  Comora  Islands,  notably  Mayotte.  The 
mountainous  islands  of  the  Gulf  of  Guinea  afford  a  few  cases. 

Thus  it  seems  that,  while  the  peculiar  geographic  distribu- 
tion of  hemoglobinuria  is  embraced  by  that  of  malaria,  it  is 
not  coextensive  with  the  latter.  And  here  the  relation  ceases. 
While  all  localities  in  which  blackwater  fever  exists  endemically 
are  highly  malarial,  there  are  very  extensive  regions  in  which 
the  severest  forms  of  tropical  malaria  are  rampant  where 
hemoglobinuric  fever  is  unknown. 

Wellman^^  maintains  a  close  relationship  between  the 
geographic  distribution  of  Myzomyia  funesta  in  Angola  and 
that  of  blackwater  fever.  Daniels^^  believes  that  if  the 
disease  is  due  to  one  or  all  of  several  varieties  of  mosquitoes 
which  he  mentions,  M.  Junestus  must  be  one  of  those  im- 
plicated. F.  Plehn-*  suggested  a  possible  relation  between  the 
geographic  range  of  hemoglobinuric  fever  and  that  of  certain 
mosquitoes. 

In  certain  localities  the  disease  seems  to  be  on  the  increase. 
Crosse'  says  that  it  is  increasing  in  certain  parts  of  West 
Africa.  Manson^^  refers  to  the  belief  of  competent  observers 
that  it  is  yearly  becoming  more  common  in  Africa.  Johnson'^ 
and  F.  Plehn  assert  that  it  is  undoubtedly  becoming  more 


2  28  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

prevalent  on  the  West  Coast  of  Africa,  and  A.  Plehn^"  believes 
that  it  is  increasing  in  frequency  in  New  Guinea.  The  in- 
habitants of  the  region  of  Jalpaiguri,  in  India,  are  recently  said 
to  be  alarmed  at  its  increase  in  that  section. ^^ 

On  the  other  hand,  there  are  places  where  it  is  becoming 
less  frequent.  The  medical  report  from  German  East  Africa 
for  the  year  1903-04  shows  a  decrease  from  the  preceding 
year.  The  report  from  Duala  shows  a  steady  annual  de- 
crease from  1901  to  1904  inclusive.^*  Kohlbrugge*  declares 
that  it  is  becoming  rarer  in  the  Malay  Archipelago.  A. 
Plehn^^  after  mentioning  the  decrease  in  certain  sections  of 
West  Africa,  prophesied  that  in  half  a  century  this  scourge  of 
Tropical  Africa  would  become,  if  not  a  historic  reminiscence, 
at  least  an  insignificant  rarity.  It  is  probably  becoming  less 
frequent  in  some  of  the  Southern  States  judging  from  my 
experience  in  Eastern  Arkansas. 

Epidemics  of  hemoglobinuric  fever  have  been  described. 
Mastermann^''  states  that  in  1893  there  was  a  regular  epidemic 
of  malaria  in  and  around  Jaffa,  and  among  the  fatal  cases  were 
a  great  many  of  hemoglobinuria.  Says  Plehn,^"  "Not  infre- 
quently the  disease  appears  in  epidemic  form,  as  was  the  case 
several  years  ago  in  Goree,  Quittah,  and  Bonny."  Sambon^ 
mentions  several  epidemics,  as  follows:  The  disease  broke  out 
among  the  laborers  employed  in  making  the  canal  through 
the  Isthmus  of  Corinth;  it  attacked  the  Chinese  laborers  on 
the  Congo  Railway;  and  in  1885,  according  to  Dr.  Wenyon,  of 
Fatshan,  China,  it  ravaged,  like  a  plague,  the  Chinese  army  on 
the  Tonquin  border  of  Kwangsi.  In  collective  dwellings — 
such  as  barracks,  hospitals,  schools — it  may  attack  several 
persons  at  the  same  time.  In  1885  it  broke  out  in  a  prison  in 
Castiades,  Sardinia,  attacking  24  out  of  800  convicts. 


CHAPTER  X 
ETIOLOGY  OF  BLACKWATER  FEVER 

Among  the  conditions  other  than  blackwater  fever,  under 
which  hemoglobinuria  can  occur,  may  be  mentioned  paroxys- 
mal hemoglobinuria,  scarlet  fever,  typhus  and  typhoid  fevers, 
acute  articular  rheumatism,  leucemia,  pneumonia,  streptococcus 
infection,  chronic  suppurative  conditions,  after  extensive 
burns  or  freezing,  occasional  injuries,  rupture  of  ectopic  preg- 
nancy, transfusion  of  blood,  injection  of  tuberculin,  poisoning 
with  phenocoll,  guaiacol,  pirodin,  salipyrin,  salicylic  acid, 
antipyrin,  sulphonal,  the  salts  of  chloric  acid,  phenol,  pyro- 
gallic  acid,  sulphuric,  nitric,  and  hydrochloric  acids,  naphthol, 
analine,  chrysarobin,  toluylendiamin,  glycerine,  nitrobenzol, 
potassium  chlorate,  phenacetin,  arseniuretted  hydrogen,  methyl- 
ene-blue,  phosphorus,  oxalic  acid,  certain  illuminating  gases, 
helvella  esculenta,  and  snake  venom.  Hemoglobinuria  is  a 
common  symptom  of  Texas  fever  in  cattle,  and  is  seen  occasion- 
ally in  sheep,  dogs,  goats,  horses,  and  mules,  following  in- 
fection with  hematozoa  resembling  the  malaria  parasite. 

Race. — Hemoglobinuric  fever  is  chiefly  a  disease  of  the 
white  race.  The  negro  is  not  absolutely  immune,  though 
not  a  few  observers  of  wide  experience  have  not  seen  cases 
in  this  race.  This  relative  immunity  can  be  explained  only 
by  natural  selection.  It  varies  markedly  in  different  tribes 
and  members  of  an  unsusceptible  tribe  may  be  attacked  on 
moving  to  a  blackwater  fever  focus.  F.  Plehn^  refers  to  an 
extensive  outbreak  that  occurred  among  the  Cameroon  negroes, 
especially  those  who  came  from  the  interior  to  the  coast. 
According  to  Dryepondt,^'  the  negroes  recruited  for  the 
Congo  Free  State  in  1890  to  1892  paid  a  large  tribute  to  this 
malady.  DeGreny^  saw  twenty  cases  in  negroes  imported  from 
the  British  Antilles  for  railroad  construction  work  on  the  lower 
Congo.  In  the  medical  report  from  German  East  Africa  for 
229 


230  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

the  official  year,  1903-04,  there  were  listed  eight  cases  in 
negroes.  Corre,^  Donny,^  the  younger  Moncorvo,'  Hanley,^^ 
A.  Plehn,'«  Rudolph  Plehn,"  Wittrock,''^  Brunn,'^  Curry,'^ 
Eyles,^^  Doering,^'  Reynolds,'"'  Easmon,-'  Wicke,^^  Gaertner,*^ 
Quartey-Papafio,-^  O'Sullivan-Beare,*^  Vieth,*^  Goltman  and 
Krauss,*-  McElroy,"^  Berenger-Feraud,^  Ziemann,^'  Fisch,^ 
Ollwig,**  Greisert,'''*  Perry, ^^  Lovelace, ^^  Dufranc,^"^  Schu- 
macher,^* JungelSj^'Hoesemann,^"  (13  cases), Lewis, ''^Francez,^^ 
Minor,*^  McKay,^*  Tyson,*'  Gorgas,^"  and  Wendland,'^  have 
seen  cases  in  negroes.  I  have  seen  two  cases  in  mulattoes  and 
two  in  black  negroes.  Chinese  imported  into  blackwater 
fever  regions  are  almost  as  susceptible  as  whites.  Manson^' 
says  that  many  of  the  Chinese  laborers  on  the  Congo  railway 
died  of  hemoglobinuric  fever.  Imported  Indians  are  affected, 
but  according  to  Daniels,^'-  are  only  about  one-fourth  as  sus- 
ceptible as  Europeans.  As  may  be  inferred  from  one  of  the 
names,  "fievre  jaune  des  Creoles,"  Creoles  are  not  infrequently 
attacked.  Masterman^*  reports  that  it  is  common  among  the 
Jews  of  Palestine.  Rothschuh^  saw  cases  in  mixed  breeds  and 
pure  Indians  in  Nicaragua. 

Sex. — Males  are  more  often  stricken  than  females,  the 
latter  being  less  often  exposed  to  malarial  infection.  In 
the  temperate  zone  the  proportion  of  males  to  females  is 
about  3  to  I.  In  persons  under  15  the  proportion  is  more 
nearly  equal.  As  we  approach  the  equator  the  difference  be- 
comes wider,  owing  to  the  relatively  small  number  of  sus- 
ceptible females  and  children.  Daniels^^  says  the  proportion 
of  male  to  female  cases  in  British  Central  Africa  is  15  to  i. 
Cardamatia^^  believed  that  pregnancy  conferred  immunity; 
however,  Krauss^^  has  reported  a  case  in  a  pregnant  woman, 
who  made  a  tedious  recovery  after  abortion.  A  few  years  ago^* 
published  brief  notes  of  a  case  occurring  in  the  practice  of 
a  colleague.  The  woman  aborted  on  the  third  day  of  the  disease 
and  died  on  the  fourth.  Cases  have  often  been  observed  to 
follow  immediately  after  menstruation. 

Age. — In  America  more  than  half  the  cases  occur  before  the 
age  of  thirty,  though  very  young  children  are  relatively  exempt. 
In  the  tropics  it  is  commoner  in  the  third  and  fourth  decades  of 


BLACKWATER    FEVER  23 1 

life  because  most  of  the  susceptible  population  is  within  these 
ages.  Daniels-^  saw  a  case  in  a  half-caste  about  five  years  old; 
Wendland,''  Van  der  Scheer^'  and  Karamitsas^^  observed  cases 
in  children  of  four;  Lipari^"  mentions  two  cases  in  children  of 
three,  Masterman'*  one  in  a  girl  of  two,  and  Oetker''^  one  in  a 
two-year-old  child;  Fisch'^  saw  cases  in  children  of  fourteen 
months  and  two  and  one-half  years,  and  McElroy^*  one  at 
twelve  months. 

Season. — In  the  tropics,  like  malaria,  it  is  perennial,  occur- 
ring without  marked  seasonal  prevalence,  though  probably 
commoner  in  the  transition  period  from  the  moist  to  the  dry 
season.  In  the  temperate  zone  it  appears  at  the  height  of,  or 
immediately  following,  the  malarial  season,  the  second  half  of 
the  year  showing  by  far  the  greater  number  of  cases,  especially 
August,  September  and  October.  A  few  cases  are  seen  in  the 
first  six  months.  In  Greece  it  is  during  the  months  of 
November  and  December  that  the  majority  of  cases  occur. 

Family  Predisposition. — Tomaselli^*  beUeved  in  a  well- 
marked  family  tendency,  having  observed  cases  in  several 
members  of  the  same  family.  Daniels^^  refers  to  three  families 
in  which  he  noticed  this  predisposition.  Three  such  families 
are  known  to  me.  Cardamatis^^  relates  the  case  of  a  family 
of  seven,  of  which  the  father,  mother,  and  one  daughter  were 
within  a  few  days  attacked  and  died  with  blackwater  fever. 
The  others,  removing  to  Athens,  were  all  subsequently  attacked 
but  fortunately  recovered.  Sutherland^^  speaks  of  a  family 
of  which  all  the  children,  six  in  number,  died  with  hemoglobi- 
nuric  fever. 

Idiosyncrasy.^An  idiosyncrasy  in  susceptible  individuals 
has  long  been  assumed  and  by  many  passively  accepted  as 
the  sole  explanation  of  the  mysteries  of  pathogenesis.  Foust- 
anos'®  holds  that  idiosyncrasy  is  either  congenital  or  acquired, 
as  the  result  of  debility  or  bodily  changes  due  to  syphilis,  malaria, 
etc.  There  is  not  sufi&cient  evidence  to  show  that  heredity 
plays  an  important  part  in  whatever  is  meant  by  this  vague 
term. 

Previous  Attacks  of  Hemoglobinixria. — Who  has  had  black- 
water   fever  is  prone   to   recurrences.     In   the   tropics   about 


232 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


one-fourth  of  the  subjects  have  more  than  one  attack.  Of 
304  cases  mentioned  by  Cardamatis,  81  occurred  in  persons 
who  had  previously  had  it.  Several  tropic  physicians  record 
repeated  attacks  in  themselves.  Thus  Y.  Plehn^'  had  five 
attacks,  Crosse'^  at  least  ten  severe  attacks,  and  Banks'^ 
twelve  or  thirteen  during  eighteen  years'  residence  in  Congo. 
One  of  Koch's''^  patients  had  ten  attacks  in  one  year,  and  the 
Plehns*"  state  that  they  know  persons  who  have  had  fifteen  or 
more  attacks.  I  treated  a  patient  in  his  twelfth  attack. 
There  is,  therefore,  no  active  immunity;  the  only  immunity 
except  natural  being  conferred  by  prolonged  residence  in  an 
endemic  focus. 

Length  of  residence  in  the  home  of  the  disease  is  an  im- 
portant factor.  A  curve  showing  the  number  of  first  attacks 
to  each  year  of  residence  would  rise  from  the  first  to  the  third 
years  and  then  fall  gradually.  This  is  almost  constant  for 
observation  in  the  tropics,  being  less  noticeable  in  temperate 
regions.  The  following  table  of  cases  seen  in  the  tropics  will 
illustrate: 


3rd   4th   5th 
year  year  year 


Burot  andLegrand,*'  100  cases 

Daniels,-'  114  cases 

Berenger-Feraud,*^  185  cases. . 
Vedy,*'  54  cases 


74       16 


Fifty  cases  observed  by  McElroy^''  in  the  Mississippi  Valley 
were  distributed  as  follows:  Two  in  the  first  year  of  residence, 
three  in  the  second,  six  between  the  second  and  the  fifth, 
twenty-three  between  the  fifth  and  tenth,  1 1  between  the  tenth 
and  twentieth,  and  five  after  twenty  years. 

Exceptionally  are  cases  seen  after  only  a  short  period  of 
tropic  residence,  as  Plehn's^  case  XXXV,  after  two  months 
in  the  Cameroon,  and  one  of  Brem's^^  cases  after  two  months 
on  the  Isthmus  of  Panama.  Ziemann*^  mentions  two  cases 
beginning  six  weeks  and  twenty-seven  days,  respectively,  after 


BLACKWATER    FEVER  233 

arrival  in  a  malaria  locality,  and  Oeconomou'^  observed  a  case 
occurring  after  ten  days  of  residence  in  a  malarial  region. 
The  case  showing  the  longest  period  of  residence  before  onset 
in  which  this  is  specified  is  that  of  Howard,*^  twenty-three 
years  in  Central  Africa,  though  in  five  of  McElroy's^*  cases  the 
length  of  residence  was  longer  than  twenty  years. 

Altitude. — Hemoglobinuric  fever  is  often  considered  a 
disease  of  the  lowlands,  though  cases  are  commonly  observed 
at  heights  of  3,000  feet.  The  results  of  Daniel's^^  observations 
on  the  influence  of  altitude  may  be  stated  as  follows: 

The  greater  number  of  recorded  cases  have  occurred  in  the 
highlands  at  or  about  3,000  feet  above  the  sea  level.  There 
are  two  reasons  for  this:  First,  the  number  of  residents  in  these 
highlands  is  much  greater  than  in  the  other  districts.  This 
correction  alone  reverses  the  figures;  secondly,  many  of  these 
cases  were  visiting  the  highlands  on  account  of  health  or  for 
other  reasons.  Others  were  passing  through  the  highlands 
when  invalided  home.  Some  had  recently  visited  the  lowlands. 
A  true  correction  that  would  attribute  each  case  to  the  district 
in  which  the  disease  was  acquired  is  impossible,  but  taking  an 
arbitrary  period  of  a  fortnight  as  representing  a  not  improbable 
latent  period  we  should  find  that  the  place  of  residence  a  fort- 
night or  more  previous  to  the  onset  would  give  a  very  different 
district  distribution  to  that  given  by  considering  the  places  of 
onset.  Corrected  by  proportional  numbers  of  susceptible 
persons  in  each  district  and  for  place  of  residence  two  weeks 
previous  to  onset,  the  distribution  per  10  of  population  is  as 
follows:  1.04  in  the  highlands,  7.28  at  the  lake  level  (Lake 
Nyassa,  altitude  about  1,500  feet),  and  3.8  in  the  lower  shore 
regions.  According  to  Laveran^'  it  was  necessary,  on  account 
of  the  frequency  of  blackwater  fever,  to  abandon  certain  posts 
in  Congo  established  at  heights  of  500  to  700  meters. 

Change  of  residence  is  a  not  uncommon  cause  for  an  out- 
break, especially  ii  the  difference  in  altitude  or  climate  is  decided. 
In  Africa  not  only  those  coming  from  the  mountains  to  the 
lowlands,  but  also  those  moving  from  the  insalubrious  littoral 
to  the  refreshing  high-lying  districts  are  predisposed.  This 
change  seems  to  be  independent  of  the  hardships  of  travel. 


234  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

After  Leaving  Endemic  Region. — Such  cases  have  been 
observed  in  England  by  Bassett-Smith,*^  Hughes, ^^  Sylivan,* 
Crosse/  Manson,^"  Daniels, ^^  and  Parker;^^  in  Ireland  by 
Mowbray;^^  in  Germany  by  Schlayer,^'  A.  Plehn,^'  Kleine,'* 
Koch,'°  and  F.  Plehn;^"  in  France  by  Burot  and  Legrand,'^ 
Le  Dantec,^'^  Kelsch  and  Kiener,^^Rouvier,^^  Vincent,'  Boison,^^ 
Troussaint^'  and  Laveran;^'  in  Belgium  by  Dryepondt  and 
Vancanpenhout^'  and  Bertrand;^°"  and  in  Baltimore  by  Brem.*^ 
Many  of  these  cases  were  not  mere  relapses;  indeed,  in  the 
majority  in  which  the  number  of  previous  attacks  was  spe- 
cifically stated  they  were  first  attacks.  The  onset  may  occur 
from  a  few  days  to  five  months  or  more  after  leaving  the  endemic 
area.  Inclement  weather  and  fatigue  seem  to  be  factors  in 
some  of  these  cases.     The  mortality  is  low. 

Occupation,  which  requires  residence  in  a  malarial  locality 
and  which  necessitates  overturning  of  the  soil,  as  gardening, 
farming,  ditching,  railroad  construction,  etc.,  is  largely  pre- 
disposing. Not  a  few  cases  occur  among  timber  workers. 
The  disease  prevailed  extensively  among  those  engaged  in  the 
construction  of  the  canal  of  Corinth.  Manson^'  tells  us  that 
many  of  the  Chinese  laborers  on  the  Congo  railroad  died  of 
hemoglobinuric  fever,  and  DeGreny'  found  many  cases  in  both 
negroes  and  whites  in  the  railroad  work  on  the  lower  Congo. 
Crosse^'  says  that  it  is  significant  that  his  first  three  gardeners 
died  of  blackwater  fever,  and  that  for  some  considerable  time 
cases  occurred  only  near  the  plantations,  and  as  the  plantations 
became  more  numerous  the  disease  spread  to  the  other  stations 
in  the  territories. 

Occasional  Causes. — Of  these,  exposure  to  cold  and  dampness 
is  probably  the  most  efficacious,  showing  somewhat  analogous 
to  paroxysmal  hemoglobinuria.  Over-exertion  precedes  some 
cases.  The  influence  of  alcohol  has  probably  been  over-esti- 
mated. Trauma  has  a  slight  etiologic  importance.  Thus 
Mould^"^  mentions  a  case  developing  after  a  sprained  ankle; 
Plehn'"  one  in  which  a  man  was  wounded  in  a  bush  fight  and 
bled  considerably.  Crosse''^  and  Plehn  saw  cases  immediately 
following  confinement.  Psychic  states,  as  anger,  grief,  and 
fear,  exposure  to  sun,  fatigue,  excessive  venery,  syphilis,  and 


BLACKWATER    FEVER  235 

the  mercury  cure  have  been  mentioned  as  occasional  causes. 
Cardamatis^^  lays  stress  on  the  association  with  rheumatic 
diathesis,  1 2  of  his  30  cases  being  rheumatic.  Alexander  Haig^"^ 
believes  there  is  an  intimate  relation,  most  probably  causative, 
between  an  excess  of  uric  acid  in  the  blood  and  hemoglobinuric 
fever.  He  makes  the  unfounded  statement  that  the  ordinary 
acid  sulphate  of  quinine  is  about  one-fifth  xanthin,  which  is 
physiologically  and  pathologically  equivalent  to  uric  acid,  and 
herein,  he  believes,  lies  its  supposed  power  to  produce  hemo- 
globinuria. Johnson^^  holds  that  a  meat  diet  predisposes  to 
blackwater  fever. 

Previous  Malaria. — It  may  be  said  with  almost  absolute 
certainty  that  previous  infection  with  malaria  is  essential. 
In  fact,  a  majority  of  careful  observers  make  the  unqualified 
assertion.  The  extreme  rarity  of  cases  in  which  preceding 
malarial  infection  is  denied  almost  forces  us  to  the  conclusion 
that  it  may  have  been  overlooked,  as  might  occur  in  latent 
or  masked  infection.  It  is,  however,  not  impossible  that  hemo- 
globinuria may  exceptionally  accompany  the  first  outbursts  of 
malaria,  as  in  cases  of  F.  Plehn,^  Goltman  and  Krauss,*- 
and  Brem.^^  In  all  of  the  cases  of  Tomaselli  and  Koch,  the 
most  ardent  advocates  of  the  quinine  theory,  there  was  history 
of  antecedent  malaria.  Tomaselli^^  states  in  italicized  words 
that  the  two  conditions  which  favor  the  hemolytic  action  of 
quinine  are:  i,  malarial  infection,  chronic  or  sometimes  recent; 
2,  a  special  idiosyncrasy,  often  hereditary. 

Cardamatis^^  cites  several  writers  who  have  seen  cases 
without  preceding  malaria,  and  Van  der  Scheer^^  is  said  to 
have  seen  such  a  case. 

Pathogenesis. — There  are  three  chief  theories  as  to  the  nature 
of  hemoglobinuric  fever;  i,  that  it  is  malaria;  2,  that  it  is  quinine 
poisoning;  3,  that  it  is  a  disease  sui  generis. 

I.  Against  the  malarial  nature  of  hemoglobinuric  fever  may 
be  urged  the  following  objections: 

I.  The  parasites  are  often  absent;  when  present  they  are 
not  numerically  proportionate  to  the  severity  of  the  attack 
and  usually  disappear  as  the  disease  progresses;  sporulation 
does  not  correspond  in  time  with  the  symptoms;  hemoglobin- 


236  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

uria  may  be   associated   with   different  forms  of  the  malaria 
parasite. 

2.  In  malaria  very  numerous  parasites  may  be  present  with- 
out producing  hemoglobinuria. 

3.  The  geographic  range  does  not  coincide  with  that  of 
malaria. 

4.  Its  seasonal  prevalence  does  not  correspond  with  that 
of  malaria. 

5.  Blackwater  fever  is  not  amenable  to  quinine. 

The  frequency  with  which  the  parasites  are  found  is  shown 
by  the  following  list  of  examinations  by  various  observers. 
The  first  column  of  figures  shows  the  number  of  examinations 
made,  the  second  the  number  in  which  the  parasites  were 
found : 

Kanellis^""' 20  10 

Bignami  and  Bastianelli^"'' 2  i 

Vincent' 5  i 

Drypondt  and  Vancanpenhout'" i  o 

PowelU"? II  5 

Koch" 16  2 

Hanley'* 13  o 

Cardamatis'"^ 25  4 

Burns" 3  3 

Boison^' 3  3 

Daniels^' 16  4 

Wellman'" i  i 

Crosse"" i  i 

Brem'^ 14  2 

Krauss'"* 11  7 

McElroy'* 23  9 

Thin"" I  o 

Kleine« 15  6 

Hoffman'^ 3  2 

Curry'i" 2  o 

Troussaint^' 7  s 

Pezopoules  and  Cardamatis^' 7  3 

Ketchen'i' i  i 

Masterman''' i  i 

Schlayer'^ i  i 

OUwig^' IS  6 

Stephens  and  Christophers^' 16  3 

Howard" i  o 

Ruge''^ I  I 

Goltman  and  Krauss'^ 12  4 


BLACKWATER    FEVER  237 

Hartsock'^' i  o 

F.  Plehn' S3  22 

Broden'" 20  6 

Marchoux''^^ 9  i 

Oeconomou^'* 3  o 

Cardamatis^'* 25  4 

Le  Dantec"' 3  o 

Bernardo'^''' 20  17 

Gauducheau^'^ 15  o 

Da  Costa"* 20  15 

Grattan"' 11  4 . 

Kulz-" 16  3 

Kudicke" 17  9 

Wellman"' 34  3 

Lovelace"* 327  145 

Woldert" 21  2 

Deaderick''^ 34  14 


Total 861  331 

As  stated  in  the  first  objection,  the  parasites  when  present 
tend  to  disappear  as  the  disease  progresses.  The  following 
figures  show  the  difi'erence  in  results  of  examination  at  dif- 
ferent periods.  The  great  frequency  with  which  they  are 
found  the  day  before  the  attack  should  be  noted: 

Stephens  and  Christophers:'-" 

Day  before  attack  parasites  present  in  95  per  cent,  of  cases. 

Day  of  attack  parasites  present  in  70  per  cent,  of  cases. 

Day  after  attack  parasites  present  in  20  per  cent,  of  cases. 
Mannaberg 


inaDerg:"^ 

Day  before  attack  parasites  present  in  95.6  per  cent,  cases. 
Day  of  attack  parasites  present  in  63  per  cent,  of  cases. 
Day  after  attack  parasites  present  in  17.1  per  cent,  of  cases. 

The  reasons  for  the  rapid  disappearance  of  the  organisms 
are,  first,  that  often  quinine  has  been  taken  before  the  examina- 
tion; secondly,  that  in  the  terrific  hemolysis  the  weaker  cells, 
including  those  containing  parasites,  are  usually  the  first  to 
succumb. 

The  hemoglobinuria  occurring  in  Texas  fever  of  cattle  is 
cited  with  some  show  of  reason  as  an  argument  for  the  purely 
malarial  origin  of  blackwater  fever.  There  are  essential  dif- 
ferences, however,  in  the  occurrences  of  blackwater  in  malaria 
and  Texas  fever.     First,  malaria  is  followed  by  blackwater  in  a 


238  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

very  small  percentage  of  cases,  malaria  being  common,  hemo- 
globinuria fever  much  rarer;  in  Texas  fever  blackwater  is  a 
common  symptom,  occurring  in  nearly  all  severe  cases. 
Second,  in  blackwater  fever  in  man  the  number  of  parasites 
shows  no  proportion  whatever  to  the  severity  of  the  disease. 
In  Texas  fever,  on  the  other  hand,  as  is  shown  by  Smith  and 
Kilbourne*^^  the  number  of  parasites  is  in  direct  relation  to  the 
severity  of  the  process  and  increases  as  a  fatal  termination  ap- 
proaches. In  human  malaria  the  parasites  may  exist  in  very 
large  numbers  without  the  development  of  hemoglobinuria; 
this  is  not  the  case  in  Texas  fever.  Bonome  found  in  the  icter- 
hemoglobinuria  of  sheep  the  same  relation  between  the  number 
and  behavior  of  the  hematozoa  and  the  intensity  and  progress 
of  the  attack  as  obtains  with  Texas  fever. 

The  form  of  parasite  found  in  blackwater  fever  is,  in  the 
great  majority  of  instances,  the  estivo-autumnal.  Only  ex- 
ceptionally is  hemoglobinuria  combined  with  infections  with 
the  benign  organisms.  The  tertian  parasite  has  been  observed 
in  cases  of  Ziemann,*^  Panse,*^  Orme,^^'  Pecori,^^^  Carducci,^^^ 
Van  der  Horst,^  Cardamatis*^  (15  cases),  Deeks  and  James*^ 
(21  cases),  Williamson, ^^  Roseo,*'  Hughes,^'  Koch^"^  (5  cases), 
A.  Plehn^®  (3  cases) ,  Ollwig,'^  McElroy,^*  Goltman  and  Krauss,^^ 
Brem,^^  Herrick,^^  and  CurP^  (3  cases).  The  quartan  parasite 
has  occurred  in  cases  of  Vincenzi,^^  Groco,*^  Kleine,'^  Kudicke,^* 
Christophers  and  Bentley,*^  Cardamatis^*  (5  cases),  and  Otto.^^ 
Thiroux^^  and  Laveran^'  are  said  to  have  found  the  large  form 
of  parasite,  but  whether  tertian  or  quartan  is  not  stated.  The 
fact  that  parasites  other  than  estivo-autumnal  have  been  found 
is  no  argument  against  the  malarial  nature  of  blackwater  fever, 
since  cases  of  pernicious  malaria  in  which  only  the  large  tertian 
parasites  were  found  have  been  reported  by  French, ^^^  Ewing^^* 
(2  cases),  Ziemann*^  and  others. 

Some  writers  believe  that  in  addition  to  the  mechanical  de- 
struction of  the  red  cells  by  the  parasites  the  latter  give  off  toxins 
which  have  hemolytic  powers.  The  facts,  however,  that  in- 
tense hemolysis  may  occur  with  very  few  parasites  in  the  blood, 
and  that  the  parasites  when  present  do  not  bear  a  direct  rela- 
tion to  the  severity  of  the  disease,  but  rapidly  diminish  as  the 


BLACKWATER    FEVER  239 

disease  progresses,  speak  strongly  against  the  role  of  a  parasitic 
toxin  in  blackwater  fever. 

The  number  of  cases  in  which  the  parasite  is  found  if  the 
examination  is  made  early  constitutes  a  conclusive  evidence 
of  an  intimate  relationship  to  malaria.  This,  however,  is  not 
all.  The  testimony  furnished  by  the  parasites  is  corroborated 
by  the  two  subsidiary  evidences  of  malaria:  first,  pigmented 
leucocytes;  secondly,  mononuclear  leucocytosis.  Given,  there- 
fore, the  presence  of  the  parasites  in  the  first  hours  of  attack, 
and  the  almost  constant  finding  of  pigmented  leucocytes  and 
mononuclear  leucocytosis,  it  is  impossible  to  deny  that  malaria 
plays  an  important  role  in  its  production. 

The  peculiarity  of  the  geographic  distribution  of  hemo- 
globinuric  fever  is  no  argument  against  its  malarial  nature. 
While  it  does  not  occur  in  all,  even  highly,  malarial  countries, 
it  is  not  met  except  in  markedly  miasmatic  regions.  Neither 
does  the  distribution  of  quartan  fever  or  some  forms  of  per- 
nicious fever  coincide  with  that  of  malaria  in  general;  nor  is 
the  slight  difference  of  seasonal  prevalence  of  any  weight.  The 
different  forms  of  malaria  have  different  seasons  of  prevalence 
as  "spring  tertian,"  and  estivo -autumnal. 

Favorable,  therefore,  to  malarial  character  are: 

1.  Geographic  distribution. 

2.  Length  of  residence  in  endemic  region. 

3.  Previous  attacks  of  malaria. 

4.  Malarial  prophylaxis  is  prophylactic  of  blackwater 
fever. 

5.  Blood  findings;  parasites,  pigmented  leucocytes,  mono- 
nuclear leucocytosis. 

The  fact  that  hemoglobinuric  fever  does  not  respond  to 
quinine  is  one  of  the  strongest  evidences  that  it  is  not  an 
attack  of  malaria  per  se. 

My  opinion  of  the  relation  of  malaria  to  blackwater  fever 
is  that  the  former  is  essentially  and  solely  the  predisposing 
cause,  and  that  in  some  cases  it  may  act  also  as  the  exciting 
cause. 

II.  Tomaselli  first  published  his  observations  as  to  the 
etiologic   relation   between   quinine   and   blackwater   fever  in 


240  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

1874.  More  recently  Koch  has  directed  attention  to  it. 
The  widespread  controversy  that  followed  the  publication  of 
Koch's  views  was  bitter  in  the  extreme;  the  matter  was  even 
aired  in  the  London  lay  press.  The  misunderstanding  was 
probably  due  to  two  causes:  first,  ignorance  of  Koch's  utterance 
at  first  hand;  secondly,  the  somewhat  non-committal  manner 
in  which  he  expresses  his  idea  of  the  relation  to  malaria.  While 
he  is  very  emphatic  that  blackwater  fever  is  not  an  attack  of 
malaria,  he  is  not  clear  as  to  the  predisposing  role  of  the  latter. 
He  does  not  even  assert  that  quinine  is  the  exciting  cause  in  all 
cases,  but  admits  that,  although  he  saw  no  cases  of  black- 
water  fever  in  which  quinine  could  be  excluded,  he  could  not  go 
so  far  as  to  maintain  that  every  case  of  blackwater  fever  is 
quinine  poisoning.  There  is  no  doubt  but  that  this  acrid  dis- 
pute was  productive  of  dire  results,  inasmuch  as  it  brought  the 
specific  into  discredit  not  only  with  the  laity,  but  with  many 
of  the  profession.  Even  yet  it  is  necessary  in  some  places  on 
account  of  a  fear  of  hemoglobinuria  to  disguise  quinine  before 
it  can  be  given. 

Tomaselli^*  was  able  to  collect  from  the  literature  only  102 
cases  of  quinine  hemoglobinuria. 

The  objections  to  the  quinine  theory  are: 

1.  Hemoglobinuria  is  restricted  in  geographic  range,  and 
is  absent  from  some  highly  malarial  localities  where  much 
quinine  is  used. 

2.  Hemoglobinuria  does  not  follow  the  administration 
of  quinine  for  maladies  other  than  malaria. 

3.  In  a  considerable  number  of  cases  the  antecedent  use  of 
quinine  can  be  eliminated  with  certainty. 

4.  The  same  individual  may  have  an  attack  following 
the  administration  of  quinine,  and  later  take  it  without  harm- 
ful results. 

5.  The  severity  of  the  attack  bears  no  relation  to  the  size 
of  the  dose. 

6.  One  dose  of  quinine  could  not  cause  intermittent  hemo- 
globinuria. 

7.  The  great  majority  of  cases  recover  even  under  the 
continued  use  of  large  doses  of  quinine. 


BLACKWATER    FEVER  241 

Objections  i,  2,  and  6  go  to  demonstrate  that  other,  and 
probably  more  important,  factors  than  quinine  are  at  work 
even  in  cases  often  attributed  to  it.  Objections  4  and  7  are 
not  potent  if  we  assume  that  only  a  portion  of  the  erythrocytes 
are  susceptible  to  the  effects  of  quinine,  and  that  all  these 
are  destroyed  by  the  first  dose.  Objection  5  proves  that  in 
cases '  where  an  outbreak  occurs  after  quinine  it  cannot  be 
regarded  as  mere  quinine  poisoning.  The  third  is  the  strong- 
est argument  against  the  theory  that  all  blackwater  fevers  are 
cases  of  quinine  poisoning.  That  quinine  is  not  always  the 
exciting  cause  is  fully  attested  by  the  numerous  cases  in 
which  no  quinine  had  been  given,  as  observed  by  Boye,^^ 
VedyjS^'  Doering,!''^  Bolden,""*  Ellenbeck-Hilden,i-"'  Legrain,i" 
Grall,i28  Rossoni,i2«  F.  Plehn,"  A.  Plehn"  (22  cases),  Mar- 
chiafava,^"^  Celli,^"^  Bastianelli,^'"'  Beyfuss,^"^  VanderScheer,^"^ 
Seal/'"  Powell,"^  Von  Diesing,!""^  Carre/o^  Schellong,"'^ 
Laveran,^*  Quennec,^"^  Navarre,^"^  Reynolds/"^  Etienne,^°* 
Sims,!"^  Donny,i°5  Dryepondt,i°^  Mense,i°2  Rothschuh,^  Fluit,^ 
R.  Plehn,"  Dempwolff,"  Crosse,^"  Thin,i°»  Stalkarrt,"i 
Christophers  and  Bently,*'  Dufranc,^^  Decks  and  James,^^  Con- 
nor," Sutton,«»  Hopkins,"^  Cargill,!"  Mould,"i  Hoffmann," 
Daniels, ^^  Rankin,i'^  Cardamatis^^  (32  cases),  Yofe,^^  Mof- 
fatt,i5*  Schlayer,83  Curry,"**  McElroy,"^  DuBose.i^"  Hearsey,i" 
Ziemann,^^  Brem,'^  Bignami,^"^  Doering,^^  and  Shropshire^^* 
(15  per  cent,  of  his  cases).  I  have  seen  four  cases  where  qui- 
nine could  be  excluded  from  the  etiology. 

Hemoglobinuric  fever  occurring  only  in  malarial  subjects 
and  quinine  being  specific  for  malaria,  it  is  but  a  most  natural 
sequence  of  events  that  a  large  number  of  the  cases  of  hemo- 
globinuric fever  have  developed  after  the  administration 
of  quinine.  The  bare  fact  that  blackwater  fever  often  follows 
quinine  is  weak  evidence  for  quinine  etiology  in  the  face  of  the 
numerous  cases  in  which  previous  quinine  could  be  absolutely 
excluded. 

When,    however,    attacks   can   be   produced   repeatedly    at 

will  by  a  dose  of  quinine  the  question  assumes  a  very  different 

aspect.     Such  cases  are  those  of  Murri,"^  Hoffman, ^^  Koch,'^ 

Manson,^'*    Ketchen,"i    Hopkins, ^''^    Bertrand,i°°  A.  Plehn," 

16 


242  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Ollwig,^'  Marsden/'"'  Daniels,^''  Kleine,'^  Tomaselli,"^  Vin- 
cenzi,*^  and  Grocco.*^ 

As  stated  above,  there  is  no  relation  between  the  amount  of 
quinine  and  the  intensity  of  the  attack.  Ketchen^^^  precipi- 
tated an  attack,  experimentally,  with  i}^  grains.  This  patient 
stated  that  ifg  gram  had  previously  produced  blackwater. 
Karamitsas,-^  Chomatianos,^^  Pampoukis,-^  Kanellis,-^  Koch,^^ 
KJeine,'^  Shropshire,"^  Moscato,^^  A.  Plehn,-^  Boxer,'*^  and 
others  report  outbreaks  elicited  by  less  than  l^  gram.  Panse^^ 
believes  the  usual  dose  preceding  an  outbreak  to  be  from 
}{q  to  I  gram.  Tomasehi^*  has  observed  attacks  to  follow  the 
administration  of  doses  as  small  as  from  }^o  to  }{q  gram,  and 
Koch^-°  reports  a  case  after  3^10  gram  has  been  administered. 
Kudicke,*^  and  Marchiafava  and  Bignami"  state  the  minimum 
quantity  as  i^^o  gram,  Laveran^^  and  Ziemann*^  as  i  centigram, 
and  Ruge^^  as  i  milligram. 

TomaseUi'^''  examined  various  preparations  of  quinine  to 
ascertain  whether  the  toxic  effect  was  dependent  upon  adultera- 
tion, and  concluded  that  such  was  not  the  case,  but  that  the 
toxic  properties  were  inherent  to  quinine  itself  and  to  all  the 
preparations  containing  quinine. 

The  time  intervening  between  the  administration  of  quinine 
and  the  onset  of  hemoglobinuria  is  almost  uniformly  fixed  by 
observers  at  from  one  to  six  hours.  With  six  hours  as  the 
maximum  interval,  the  cases  really  due  to  quinine  would 
dwindle  considerably. 

It  is  beUeved  by  some  writers  that  quinine  hypodermically 
does  not  produce  blackwater,  even  in  persons  susceptible,  when 
administered  orally.  This,  however,  is  not  the  case.  Toma- 
selli"  has  shown  that  subcutaneous  injections  of  quinine  are 
followed  more  promptly  by  hemoglobinuria  than  is  the  oral 
administration.  Kohlbrugge'*  thinks  that  only  the  inorganic 
salts  of  quinine  are  toxic,  and  states  that  the  tannate,  even  in 
the  largest  doses  given  to  susceptible  persons,  fails  to  cause 
hemoglobinuria.  LIcKay"-  has  recently  attempted  to  show 
that  hemolysis  following  the  administration  of  the  sulphate  of 
quinine  is  due  to  the  sulphate  and  not  to  the  quinine.  This 
view,  however,  is  not  supported  by  ch'nic  experience.     Further- 


BLACKWATER    FEVER  243 

more,  the  results  of  experiments  upon  which  McKay  based  his 
conclusion  could  not  be  verified  by  Christophers  and  Bentley. 
It  is  probable  that  neither  the  mode  of  administration  nor  the 
preparation  used,  if  absorbed,  gives  any  difference  in  results. 

The  role  of  quinine  in  hemoglobinuric  fever  is  probably 
highly  complex.  It  will  be  shown  that  it  is  of  value  as  a  pro- 
phylactic when  systematically  employed;  if  not  thus  used,  and 
malarial  infection  be  permitted  to  occur,  it  may,  in  some  persons 
thus  predisposed,  act  as  the  exciting  cause.  In  the  attack 
itself  it  is  possibly  of  value  in  destroying  the  parasites  when 
these  are  present,  or  it  may  act  harmfully  in  aiding  hemolysis. 

Even  after  a  careful  study  it  is  not  easy  to  define  precisely 
the  respective  potency  of  malaria  and  quinine  as  etiologic 
factors.  To  quote  Shropshire,"*  "To  establish  the  cause 
of  any  disease  we  must  apply  the  agent  to  the  subject,  and  have, 
as  uniform  result,  the  disease.  But  if  there  are  two  agents 
suspected  as  causative  which,  applied  together,  produce  the 
disease,  but  applied  separately  to  the  same  individual,  the  one 
produces  it,  the  other  never,  we  can  attribute  only  to  the  one  a 
causative  place,  and  to  the  other  an  accidental  presence. 
Such  is  the  case  before  us.  Malaria  taken  as  the  cause  and 
applied  without  quinine  to  an  individual  of  such  tendency, 
hemoglobinuria  results  in  15  per  cent,  of  the  cases  before  us. 
Quinine  has  probably  been  applied  to  all  the  cases  before  us 
without  the  presence  of  malaria  and  no  hemoglobinuria  result- 
ing.    Which  produces  it?" 

Favoring  malaria  as  against  quinine  we  have: 

1.  Antecedent  malaria  essential. 

2.  Relative  immunity  of  the  negro.  Racial  immunity  to 
disease  well  known;  racial  susceptibility  to  drugs  rare  or  un- 
known. 

3.  Occurs  often  without  the  administration  of  quinine. 

We  may  safely  conclude  that  the  predisposing  cause  is  always 
malaria;  the  exciting  causes  are  fresh  malarial  invasion,  quinine 
or  other  medicaments,  exposure,  exertion,  mental  states,  etc. 

III.  The  most  enthusiastic  champions  of  the  view  that 
blackwater  fever  is  neither  malaria  nor  quinine  poisoning,  but 
a  disease  sui  generis,  are  Sambon^"*^  and  Craig.  ^^^     Manson"'' 


244  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

formerly  advocated  this  theory.  The  two  reasons  for  his 
belief  are  a  similarity  to  paroxysmal  hemoglobinuria  and  an 
analogy  with  Texas  fever.  Stalkarrt/^^  Rho/^^  Vincent/ 
and  others  beheve  that  it  is  a  distinc  tdisease.  While  the 
similarity  to  paroxysmal  hemoglobinuria  cannot  be  denied,  the 
relation  to  Texas  fever,  as  we  have  seen,  is  far  from  close,  and 
the  evidence  that  it  is  a  disease  sui  generis  is  inadequate. 
Yersin"'  found  bacilli  in  the  casts  and  epithelium  in  the  urine 
of  two  patients,  and  beheved  that  he  had  discovered  the  cause 
of  the  disease.  Breaudat,"^  however,  showed  that  these  were 
the  Bacillus  coli  communis. 

Collet"^  has  recently,  without  grounds,  however,  suggested 
that  there  may  be  a  causal  relation  between  the  Bacillus 
Megatherium  and  blackwater  fever. 

The  theory  that  green  beans  and  their  blossoms  were  the 
cause  of  many  cases  of  hemoglobinuric  fever  seems  to  have 
perished  in  Greece,  Sicily,  and  Sardinia,  where  it  originated. 

It  is  generally  conceded  that  hemoglobinuric  fever  consists 
of  a  destruction  of  red  blood-cells  so  widespread  that,  the 
liver  being  powerless  to  transform  the  liberated  hemoglobin 
into  bile  pigment,  the  greater  part  is  excreted  by  the  kidneys. 
This  conversion  into  biliary  coloring  matter  is  the  physiologic 
fate  of  free  hemoglobin,  and  indeed  its  pathologic  destiny  up 
to  a  certain  Hmit  which,  according  to  Ponfick's  postulate,  is 
the  destruction  of  one-sixth  of  the  entire  number  of  red  cells — 
beyond  which  hemoglobinuria  ensues.  This  much  seems  to  be 
rather  unanimously  accorded.  The  nature  of  the  hemolysin 
is  the  missing  hnk'  in  the  pathogenetic  chain. 

Several  years  ago  I  expressed  the  belief  that  the  hemolytic 
agent  was  neither  a  specific  parasite,  a  parasitic  toxin,  nor 
quinine,  and  quote  the  following  from  my  paper  i^"^ 

"The  modern  study  of  immunity  and  cytolysis  has  thrown  a 
flood  of  light  on  hemolysis.  It  is  unnecessary  to  review  in 
detail  the  development  of  our  knowledge  of  hemolysis,  but  the 
following  facts  will  be  recalled.  It  has  been  known  for  some 
time  that  the  serum  of  certain  animals  has  the  power  of  dis- 
solving the  blood  corpuscles  of  certain  other  animals.  Bordet 
showed   that   this   effect  may  be  produced   artificially.     The 


BLACKWATER    FEVER  245 

serum  of  guinea-pigs  naturally  has  no  hemolytic  effect  on  the 
red  cells  of  the  rabbit,  but  if  the  rabbit's  blood  is  injected 
into  the  guinea-pig  and  the  process  repeated  the  serum  of  the 
guinea-pig  becomes  hemolytic  toward  the  rabbit.  It  has  been 
shown  that  the  hemolysins  are  formed  by  the  interaction  of  two 
substances:  one,  the  amboceptor  or  immune  body,  resisting 
moderate  degrees  of  heat;  the  other,  called  the  complement, 
inactivated  by  a  temperature  of  about  55°C.  Neither  ambo- 
ceptor nor  complement  alone  is  suihcient  to  dissolve  erythro- 
cytes, but  for  this  it  is  necessary  for  both  to  act,  the  am- 
boceptor sensitizing  the  cells  for  the  complement.  The  ambo- 
ceptor may  act  alone,  but  the  cells  will  only  be  rendered 
susceptible,  not  dissolved.  The  complement  has  no  effect 
whatever  on  the  red  cells  except  through  the  immune  body. 
The  complement  exists  in  normal  serum." 

Bignami^'  states  his  theory  as  follows: 

I.  An  alteration  in  the  plasma  which  is  effected,  little  by 
little,  as  a  consequence  of  a  specific  change  in  the  red  blood 
corpuscles  through  which  a  certain  number  of  them  come 
to  behave,  in  respect  to  the  organism,  hke  the  corpuscles  in 
the  blood  of  another  species  of  animal.  2.  The  formation,  in 
consequence  of  this  change,  of  a  substance  in  the  plasma  which 
is  capable,  under  certain  conditions,  of  becoming  hemolytic. 

At  the  1910  meeting  of  the  American  Society  of  Tropical 
Medicine  I  suggested  that  the  hemolysis  might  be  a  phenome- 
non of  anaphylaxis. 

It  is  possible  that  the  death  of  a  brood  of  parasites,  either 
spontaneously  or  as  a  result  of  the  administration  of  quinine, 
might  sensitize  the  corpuscles,  which  after  an  appropriate 
interval  become  hemolyzed  by  a  second  setting  free  in  the 
circulation  of  strange  proteid  from  dead  parasites.  Proteid 
anaphylaxis  is  the  only  explanation  for  a  number  of  bacterial 
diseases  and  it  is  known  to  occur  with  helminths,  for  instance 
ascaris  lumbricoides. 

It  is  believed  that  this  hypothesis  explains  the  occurrence 
of  hemoglobinuric  fever  during  and  after  malarial  infection, 
with  or  without  the  administration  of  quinine;  it  explains  why 
the  malarial  attack  may  precede  by  months  the  appearance 


246  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

of  blackwater;  why  exposure,  exertion,  etc.,  may  elicit  an  attack; 
why  the  hemolysis  does  not  always  coincide  in  time  with  the 
sporulation  of  the  parasites  in  the  case  in  which  the  latter  are 
present;  it  accounts  in  a  measure  for  the  complex  relation  with 
quinine  and  explains  quinine  fever,  post-malarial  secondary 
fever,  and  post-hemoglobinuric  fever. 

Christophers  and  Bentley,^^  constituting  a  committee  ap- 
pointed by  the  government  of  India  to  conduct  an  inquiry 
regarding  the  nature  of  blackwater  fever,  have  recently  pub- 
lished an  extensive  monograph  containing  a  record  of  their 
experiments  and  the  conclusions  which  they  reached  as  a  result 
of  these  experiments.  They  exclude  parasitic,  osmotic,  and 
chemic  actions  as  causes  of  hemolysis,  and  show  that  the  hemo- 
lysin is  probably  derived  from  auto-immunization  against  the 
organism's  own  red  cells — an  autolysin. 

According  to  the  conditions  of  its  occurrence,  hemoglobinuric 
fever  is  classified  by  the  Italian  school  as  follows : 

1 .  Malarial  hemoglobinuria : 

(a)  Cases  in  which  the  blood  contains  parasites. 

(b)  Cases  in  which  no  parasites  are  present. 

2.  Quinine  hemoglobinuria  in  malarial  subjects,  occurring: 

(a)  During  the  malarial  attack. 

(b)  After  the  attack  (post-hemoglobinuric). 


CHAPTER  XI 
PATHOLOGY  OF  BLACKWATER  FEVER 

The  pathologic  findings  vary  in  proportion  to  the  proximity 
and  intensity  of  the  malarial  attack.  In  addition  to  the 
changes  characteristic  of  malaria  there  are  found,  in  blackwater 
fever  subjects,  the  results  of  hemoglobinemia  and  polycholia 
chiefly  in  the  kidneys  and  liver.  Occasionally  post-mortems 
do  not  reveal  malarial  evidences,  as  in  two  cases  reported  by 
Curry,^'"  but  this  is  exceptional.  The  body  is  usually  deeply 
jaundiced.  There  may  or  may  not  be  edema.  The  muscular 
system  is  often  icteric. 

The  spleen  is  enlarged,  often  enormously  so,  and  congested. 
The  surface  color  varies  from  grayish  to  reddish  brown,  almost 
black.  The  capsule  is  thickened  and  usually  strips  easily,  but 
may  be  adherent.  The  consistence  of  the  organ  is  often  so 
diminished  that  it  appears  like  a  pulpy  sac.  The  trabeculae  are 
thickened  and  fibrous;  the  pulp  is  decidedly  increased.  The 
Malpighian  corpuscles  are  usually  hypertrophied,  sometimes 
giving  the  appearance  of  sago  spleen.  Pigment  is  usually 
abundant.  It  is  contained  within  the  cells  or  lying  between 
them.  The  cells  of  the  Malpighian  bodies  show  the  greatest 
quantity  and  largest  masses.  The  large  mononuclear  cells  and 
giant  cells  are  pigmented.  The  leucocytes  lying  external  to 
the  walls  of  the  small  veins  may  show  more  pigment  than  those 
scattered  here  and  there  throughout  the  pulp.  The  color  of 
the  pigment  varies  from  yellow  to  almost  black,  and  may  consist 
of  hemosiderin  or  melanin.  The  walls  of  the  smaller  vessels 
are  thickened,  and  the  lumen  may  be  obliterated.  The  sinuses 
may  be  obliterated  with  pigmented  and  other  cells.  The  endo- 
thelial cells  may  be  proliferating,  and  often  contain  granules 
of  pigment.  Parasites  and  pigmented  leucocytes  may  be 
present  in  the  spleen  when  not  discoverable  in  the  general 
circulation.  There  may  be  round-cell  infiltration  around  the 
trabeculae. 

247 


248  ENDEMIC    DISEASES    OF    THE'   SOUTHERN    STATES 

The  liver  is  enlarged,  congested  and  surciiarged  with  bile. 
It  varies  in  color  from  a  decided  yellow  to  a  dark  brown.  The 
capsule  is  slightly  adherent.  The  surface  is  usually  smooth, 
but  there  may  be  subcapsular  nodules  from  the  size  of  a  pin- 
head  to  that  of  a  pea,  which  on  section  exude  a  thick,  cheesy 
matter.  There  is  abundant  pigmentation,  often  rod  shaped, 
especially  of  the  endothelial  cells,  macrophages,  and  leucocytes. 
The  course  of  the  capillaries  may  be  well  marked  by  the  pig- 
ment contained  in  the  endothelial  cells  and  that  between  the 
wall  and  the  adjacent  liver  cells.  Both  the  yellow  and  black 
pigments  are  found,  the  former  especially,  in  the  liver  cells. 
Pigmentation  is  often  more  pronounced  in  the  center  of  the 
lobule.  Thrombi  of  pigmented  cells  in  the  capillaries  and  sub- 
lobular  veins  occur,  with  cloudy  swelling  and  fatty  degenera- 
tion of  liver  cells.  These  retrogressive  processes  are  in  the  form 
of  islands.  The  bihary  injection,  more  intense  in  the  center 
of  the  hepatic  lobule,  may  extend  to  the  smallest  branches. 
Regenerative  efforts  on  the  part  of  the  liver  cells  are  very  much 
more  common  than  in  pernicious  malaria  (Marchiafava  and 
Bignami).  Karyokinetic  barrels  and  monasters  predominate. 
This  is  interpreted  by  Bastianelli  as  evidence  of  hyperf unc- 
tion of  the  liver.  Marchiafava  and  Bastianelli  both  agree  in 
believing  that  this  multiplication  of  the  hepatic  cells  is  an 
attempt  on  the  part  of  the  liver  to  meet  the  increased  demands 
for  work  in  eliminating  the  detritus  of  hemoglobin  (Thayer). 
The  gall-bladder  is  usually  distended  with  bile. 

The  kidneys  are  generally  congested,  weigh  more,  and 
are  softer  than  normal.  The  capsule  is  loosely  attached.  On 
section  the  cortex  is  often  yellowish;  the  pyramids  may  present 
brownish  streaks,  more  intense  toward  the  apices.  In  the 
cortex  may  be'  found  wedge-shaped  hemorrhages  with  bases 
toward  the  capsule  and  apices'  pointing  toward  the  medulla. 
The  medullary  pyramids  may  show  minute  hemorrhages. 
The  glomeruli  often  escape  undamaged;  there  is  rarely  any 
pigmentation  of  the  cells  within  Bowman's  capsule;  there  may 
be  cloudy  swelling  and  slight  epithelial  desquamation.  The 
epithelia  of  the  convoluted  tubules  usually  show  cloudy  swell- 
ing, fatty  degeneration,  or  coagulation  necrosis.     There  may  be 


BLACKWATER    FEVER  249 

pigmentation  of  the  epithelial  cells.  The  lumina  are  often 
plugged  with  hemoglobin  casts  holding  the  epithelia  in  place. 
The  changes  in  the  straight  tubules  are  similar,  but  casts  are 
more  numerous.  The  epithelium  of  Henle's  loops  is  better 
presented,  but  the  lumen  is  usually  choked  with  casts  of 
hemoglobin  and  epithelial  detritus  from  the  convoluted  tubules. 
Biliary  pigment  also  occurs  here.  Karyokinesis  is  sometimes 
seen  in  the  epithelium  of  Henle's  loops  of  the  convoluted  tubules. 

The  stomach  and  intestines  may  be  negative.  The  serous 
coat  may  be  pale,  the  mucous  membrane  congested  and  bile 
stained,  especially  near  the  opening  of  the  common  bile-duct. 
There  may  be  isolated  hemorrhages,  excoriations,  and  pig- 
mentation.    The  pancreas  is  normal. 

The  pleurae  may  show  punctate  hemorrhages  and  the 
cavity  may  contain  a  quantity  of  serous  fluid.  The  surface  of 
the  lungs  may  show  slaty  specks  and  striag.  The  cut  surface  is 
very  pale,  and  exudes  a  very  small  amount  of  very  pale,  frothy, 
serous  fluid.  There  may  be  an  ashy  discoloration  in  the  course 
of  the  vessels,  hypostatic  congestion,  and  edema. 

The  pericardium  may  contain  from  a  very  few  drams  to 
several  ounces  of  a  clear  or  sanguineous  fluid,  and  may  present 
hemorrhages  varying  in  size  from  that  of  a  millet  seed  to  that 
of  a  cent.  The  heart  is  pale  and  often  flabby.  The  muscular 
fibers  are  easily  separable;  the  walls  may  be  very  thin.  The 
left  ventricle  is  usually  strongly  contracted,  the  right  col- 
lapsed. Auricles  and  ventricles  may  contain  coagula  or  thrombi. 
Microscopically  the  fibers  stain  well  and  show  striations  per- 
fectly ;  there  are  some  areas  of  slight  pigmentation  and  some  of 
connective-tissue  prohf eration ;  the  nerve  trunks  in  the  trans- 
verse section  show  marked  degeneration;  empty  nerve  sheaths 
are  seen,  and  some  connective-tissue  proliferation  into  funiculus 
(Goltman  and  Krauss). 

The  brain  is  usually  pale  and  unpigmented;  the  latter 
ventricles  may  contain  an  excess  of  fluid.  The  convexity  of  the 
pia  may  show  slight  cloudiness  in  the  course  of  the  vessels. 
The  puncta  vasculosa  may  be  scarcely  visible.  The  bone- 
marrow  shows  the  usual  changes  of  malaria.  Melanin,  hemo- 
siderin, and  proliferating  normoblasts  may  be  found. 


CHAPTER  xn 
CLINICAL  HISTORY  OF  BLACKWATER  FEVER 

After  a  severe  chill  the  temperature  rises  rapidly  and  a 
copious  discharge  of  red,  almost  black,  urine  is  voided.  The 
patient  complains  of  headache  and  pains  in  the  loins  and 
epigastrium,  and  is  afflicted  with  nausea  and  violent  bilious 
vomiting.  Thirst  is  torturing  and  insatiable  because  of  the 
gastric  disturbance.  There  may  be  more  or  less  tympanites. 
The  liver  and  spleen,  especially  the  latter,  may  be  enlarged 
and  tender.  In  a  few  hours  icterus  begins  and  the  patient 
soon  becomes  as  yellow  as  a  pumpkin.  He  is  very  restless 
and  has  an  anxious  expression.  If  the  attack  is  mild  the  dura- 
tion may  not  be  longer  than  that  of  an  ordinary  malarial 
paroxysm,  the  vomiting  ceases,  pain  disappears,  the  urine 
gradually  clears,  the  temperature  falls  to  normal  or  a  Uttle 
below,  and  the  patient  is  comparatively  comfortable  excepting 
a  degree  of  weakness.  The  jaundice  usually  lasts  a  day  or 
two  longer.  In  rare  cases  the  duration  of  the  attack  is  ex- 
tremely short,  the  urine  voided  at  a  single  act  only  being 
hemoglobinuric . 

In  severer  cases  the  temperature  may  drop,  but  not  to  nor- 
mal; vomiting  is  incessant;  urine  continues  darkly  colored  and 
becomes  scantier.  Rigors  may  occur  at  irregular  intervals, 
followed  by  a  rise  of  temperature,  deepening  of  the  color  of  the 
urine,  and  marked  prostration.  The  urine  may  become  sup- 
pressed and  death  takes  place  in  a  few  days;  or  the  patient 
may  die  suddenly  while  being  raised  to  use  the  vessel  or  to  take 
medicine  or  nourishment. 

The  attack  may  be  preceded  by  one  or  more  malarial  par- 
oxysms or  may  come  on  suddenly.  There  may  be  prodromata 
consisting  of  general  malaise,  aching  in  the  loins  and  head, 
nausea,  and  a  sHght  rise  of  temperature,  though  this  latter  may 
be  imperceptible  to  the  patient.  In  more  than  nine-tenths  of 
the  cases  the  onset  is  with  a  rigor,  usually  intense  and  pro- 
250 


BLACKWATER    FEVER  25 1 

tracted.  Sometimes,  as  in  ordinary  malaria,  the  first  stage  is 
obscure  or  wanting,  and  the  attack  begins  with  fever  and 
vomiting.  Occasionally  the  passage  of  black  water  precedes 
the  other  symptoms,  as  in  one  of  my  cases  where  the  patient 
had  had  a  mild  rigor  the  day  before  but  felt  well  enough  to  ride 
out  on  horseback  in  search  of  his  cow.  While  five  miles  from 
home  he  was  dumbfounded  at  passing  an  abundance  of  almost 
black  urine.  He  immediately  set  out  to  consult  me,  and  had 
ridden  six  miles  when  he  was  prevailed  upon  to  return  home. 
Death  from  exhaustion  occurred  on  the  fourth  day.  Rarely 
the  onset  is  characterized  by  violent  pain  in  the  abdomen. 
The  intensity  of  the  onset  is  no  guide  to  the  severity  of  the 
attack. 

There  are  four  symptoms  which  are  present  in  nearly  all 
cases.     These  are:  fever,  hemoglobinuria,  icterus,  and  vomiting. 

There  is  nothing  characteristic  in  the  temperature.  Its 
usual  range  is  from  ioi°  to  105°^.  Hyperpyrexia  is  unusual, 
though  very  high  temperatures  have  been  recorded.  Thus 
Marsden^^"  noted  a  case  in  which  the  temperature  reached 
i09°F.  Cases  in  which  the  temperature  is  normal  or  subnormal 
throughout  are  not  unknown,  for  example,  two  reported  by 
Baldwin  Seal.^^°  Neither  of  these  patients  had  taken  any 
quinine.  As  a  rule,  in  mild  cases  the  temperature  reaches  the 
fastigium  shortly  after  onset,  from  which  point  it  drops  pro- 
gressively to  or  a  little  below  normal.  In  other  cases  it  is 
intermittent,  remittent  or  irregular,  and  m_ay  resemble  the  curve 
of  septic  fever.  When  rigors  occur  during  the  course  they  are 
accompanied  by  a  rise  in  temperature.  Periodicity  is  not  a 
conspicuous  feature,  nor  is  the  characteristic  curve  of  Marchia- 
fava  and  Bignami  seen.  The  average  duration  of  the  fever  is 
from  a  few  hours  to  several  days.  The  average  in  my  cases 
was  eighty  hours.  It  usually  outlasts  the  hemoglobinuria,  but 
not  in  all  cases.  The  height  of  the  temperature  in  hemo- 
globinuric  fever  is  possessed  of  little  or  no  prognostic  import. 

A  rare  occurrence  is  the  obstinate  tenacity  or  subsequent 
rise  of  the  fever  after  hemoglobinuria  has  subsided.  The  dura- 
tion of  this  post-hemoglobinuric  fever  is  variable.  In  two  of 
Brem's*^  cases  it  was  fourteen  and  eighteen  days;  in  three  of 


252  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

my  cases  twelve,  nineteen,  and  twenty-eight  days;  in  one 
of  Bank's'^  over  five  weeks;  in  one  of  Howard's^''  six  weeks. 
Outbursts  of  hemoglobinuria  occasionally  occur  during  this 
fever.  In  most  of  the  cases  the  temperature  rose  higher  than 
during  the  hemoglobinuric  period.  It  is  entirely  um'nfluenced 
by  quinine  and  is  probably  related  to  the  spodogenous  fever  of 
Marchiafava  and  Bignami^^  or  post-malarial  secondary  fever. 
The  mortality  of  these  cases  seems  to  be  very  low. 

Schellong^^"  observed  a  pecuHar  case  which  showed  a  post- 
mortem elevation  of  temperature.  The  fever  began  to  rise 
a  few  minutes  after  death,  and  more  than  an  hour  later,  when 
last  recorded,  the  temperature  was  106. 2°F.  The  thermometer 
registered  higher  in  the  right  axilla  than  in  the  left  throughout 
the  observation. 

Probably  in  no  other  condition  do  we  see  such  rapid  and 
profound  transition  in  the  state  of  the  urine.  A  few  hours 
before  the  onset  the  urine  is  normal;  afterward  it  may  show  all 
the  characteristics  detailed  below.  In  favorable  cases  the 
return  to  normal  is  remarkable. 

The  quantity  varies  within  very  wide  limits.  In  mild 
attacks  it  may  not  vary  from  that  of  health.  Often  at  first 
there  is  an  increase,  a  decided  decrease  at  the  height  of  the 
attack,  gradually  increasing  to  normal  or  above  with  improve- 
ment. In  suppression  cases  there  is  usually  a  diminution 
from  the  first,  resulting  in  total  anuria  or  the  passage  of  a  few 
ounces  daily.  Anuria  is  due  to  the  plugging  of  the  renal  tubules 
and  to  diminution  of  blood  pressure.  Pain  resembling  that 
of  renal  colic  may  be  experienced  with  anuria.  The  tempera- 
ture may  remain  normal  throughout  suppression  of  several 
days'  duration.  It  occasionally  happens  that  urinary  secretion 
is  reestablished  after  anuria  has  persisted,  even  as  long  as 
five  days;  in  such  cases,  however,  most  die  of  comphcations 
during  convalescence.  The  outlook  is  very  grave  when  sup- 
pression lasts  longer  than  twenty-four  hours.  Death  usually 
takes  place  after  three  or  four  days,  though  Plehn^  reports  a 
fatal  case  where  life  was  prolonged  twelve  days  after  the  onset 
of  suppression,  and  Kudicke''''  observed  two  fatal  cases  in  which 
anuria  persisted  thirteen  days. 


BLACKWATER    FEVER  253 

The  color,  often  described  as  "port  wine,"  varies  from  a 
light  claret  to  that  of  black  coffee.  The  latter  color  obtains 
when  the  urine  of  a  severe  attack  is  examined  in  a  thick  layer 
by  reflected  light.  In  a  test  tube  by  transmitted  Hght  it  ap- 
pears of  a  lighter  color.  The  froth  varies  from  yellow  to 
reddish;  a  greenish  color  is  said  to  be  due  to  the  presence  of 
bile.  The  coloring  matter  is  more  often  in  the  form  of  met- 
hemoglobin,  though  oxyhemoglobin  is  found.  It  is  probably 
not  present  in  a  true  solution,  since  it  is  more  abundant  in  the 
sediment  of  a  centrifugalized  urine  than  in  the  supernatant 
fluid,  and  disappears  from  the  latter  first  with  improvement. 
The  hemoglobinuria  may  be  intermittent  or  continuous. 
Stephens  and  Christophers^-"  observed  that  blackwater  urine, 
made  alkaline  with  potash  and  then  boiled,  produced  a  purple 
color,  giving  the  bands  of  hemochromogen,  showing  that  the 
urine  itself  contained  reducing  bodies.  A.  Plehn  mentions 
that  on  boiling  the  urine  and  allowing  it  to  stand  for  some 
time  a  bright  purple  color  appears.  On  standing  an  abundant 
dirty  brownish  sediment  is  deposited,  the  amount  varying  with 
the  concentration  of  the  fluid.  The  urine  stains  Hnen  a  dirty 
red.  The  reaction  is  generally  slightly  acid,  but  may  be  neutral 
or  alkahne.  The  specific  gravity  varies  inversely  with  the 
quantity.  The  average  in  my  cases  has  been  1015.  Albumin 
is  always  present.  It  is  commonly  in  excess  of  the  hemoglobin 
and  persists  for  a  longer  period,  though  the  curves  run  more  or 
less  parallel.  Serum  albumin,  albumose,  globulin,  and  nucleo- 
albumin  are  found.  Plehn^  gives  the  Hmits  of  quantity  as 
Yl-i  grams  per  Hter,  estimated  according  to  Esbach's  method. 
I  have  very  frequently  observed  twice  as  much  as  his  maxi- 
mum limit,  and  in  one  of  my  cases  the  amount  was  14  grams 
with  the  Esbach  instrument.  Some  urines  on  being  boiled 
become  almost  completely  solidified.  Bile  is,  as  a  rule,  absent; 
it  is  never  present  in  proportion  to  the  polycholia.  It  was 
present  in  only  one  of  a  series  of  24  cases  reported  by  me.®^ 
It  was  not  found  by  the  Plehns^  or  by  Daniels"  in  any  of  their 
cases.  Urobilin  is  common.  Stephens  and  Christophers^-" 
assert  that  it  occasionally  appears  before  the  attack,  but  more 
constantly  after  the  oxyhemoglobin  has  disappeared,  or  together 


2  54  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

with  it.  In  nine  cases  I  examined  the  urine  with  negative 
results  in  all.  Marchoux^^^  maintains  that  quinine  cannot  be 
detected  in  the  urine  during  the  hemoglobinuric  period,  but 
appears  later.  But  the  observations  of  Giemsa  and  Schau- 
mann^^^  do  not  sustain  this  opinion.  They  found  the  amount 
of  quinine  excreted  during  the  attack  to  be  somewhat  larger 
than  otherwise,  and  that  the  excretion  is  extended  over  a 
longer  period  of  time  in  a  regularly  increasing  and  decreasing 
curve  which  is  uninfluenced  by  the  hemoglobin  content  of  the 
urine.  This  increased  excretion  of  quinine  in  the  urine  in 
hemoglobinuric  fever  would  lead  to  the  inference  that  the 
organism  is  not  capable,  as  it  usually  is,  of  protecting  itself  from 
the  poisonous  alkaloid  by  splitting  the  molecule.  Marchoux^^^ 
claims  that  hemoglobinuric  fever  urine  has  no  hemolytic  action 
on  the  red  blood-cells  of  normal  persons. 

On  microscopic  examination  the  field  appears  littered  with 
a  brownish  amorphous  detritus,  the  products  of  broken-down 
red  blood  corpuscles.  Whole  red  blood-cells  are  not  generally 
found  and  rarely  in  considerable  numbers.  Casts  are  abundant, 
especially  the  granular;  also  hyaUne  and  epithelial.  These 
casts  are  sometimes  almost  covered  with  the  granular  pigment. 
Renal  and  vesical  epithelium  are  common,  and  mucus  and 
crystals  of  hematoidin  may  be  found.  Leucin  and  tyrosin  are 
rare.  WiUiams,^^^  Mackey,^^^  and  Brem^^  have  described 
different  peculiar  bodies  found  in  the  urine.  The  nature  and 
significance  of  these  bodies  are  unknown. 

There  are  often  present  vesical  tenesmus  and  pain  over  the 
bladder.  Retention  of  urine,  burning  in  the  urethra,  and 
tenderness  over  the  kidneys  are  not  uncommon  symptoms. 
The  urine  may  be  voided  drop  by  drop. 

After  a  few  hours  jaundice  begins  to  appear  and,  except  in 
the  mildest  cases,  develops  rapidly  until  the  skin  and  sclera  are 
of  a  pronounced  saffron  yellow.  It  usually  outlasts  the  fever 
a  few  days.  Itching  of  the  skin  is  not  common.  Herpes  is 
relatively  infrequent  and  petechise  are  rare.  The  occurrence 
of  the  latter  is  said  to  imply  a  grave  prognosis.  Edema  or 
anasarca  may  be  encountered,  especially  in  cases  where  there 
is  unusual  involvement  of  the  kidneys.     Sweats  may  occur  with 


BLACKWATER    FEVER  255 

the  decline  of  the  fever  or  with  collapse.  The  skin  is  often  dry. 
Sometimes  the  perspiration  is  charged  with  the  pigment. 
Banks^^  mentions  a  peculiar  odor  emanating  from  blackwater 
fever  patients.  He  claims  that  it  enables  one,  together  with 
the  expression,  to  make  a  diagnosis  before  the  urine  is  ex- 
amined. So  far  as  I  know  he  has  not  been  corroborated,  though 
in  suppression  cases  a  uremic  odor  may  be  perceptible.  Herpes 
was  not  observed  in  any  of  my  cases. 

Vomiting  is  usually  one  of  the  earliest  symptoms  and  fre- 
quently the  most  distressing.  After  the  stomach  contents  are 
voided  the  vomit  consists  of  a  yellowish  or  green  bile.  Oc- 
casionally it  is  a  grass  green  or  peculiar  bluish  green,  or  it  may 
be  very  dark,  almost  black,  somewhat  resembhng  the  black 
vomit  of  yellow  fever.  The  vomiting  is  independent  of  the 
taking  of  food,  and  is  probably  more  or  less  of  central  origin. 
In  very  mild  cases  vomiting  may  be  very  insignificant  or  absent. 
Nausea  is  usually  in  proportion  to  the  vomiting.  The  bowels 
may  be  constipated  or  there  may  be  a  bilious  diarrhea.  Oc- 
casionally the  dejections  are  thin  and  watery,  of  a  reddish- 
brown  color,  and  may  closely  resemble  the  urine.  This  is 
thought  to  be  due  to  the  extravasation  of  hemoglobinuric  serum 
into  the  intestine,  and  is  usually  seen  in  severe  cases  only. 
Dysenteric  symptoms  are  infrequent.  Hemorrhage  from 
stomach  or  bowel  is  rare.  Meteoiism  is  not  an  infrequent 
symptom.  There  may  be  severe  colicky  pains  in  the  abdomen. 
Pain  is  usually  present  in  the  epigastrium  region  or  over  the 
liver  and  spleen.  These  are  usually  tender,  the  spleen  often 
greatly  enlarged,  the  liver  less  so.  The  appetite  in  all  but 
mild  cases  is  completely  lost.  Thirst  is  intense  and  cannot 
be  alleviated  for  the  vomiting.  The  tongue  is  anemic  and 
heavily  coated.  Sordes  of  the  teeth  and  lips  are  often  seen  in 
extreme  cases.  The  saliva  may  stain  the  Hnen  a  brownish 
yellow. 

The  pulse  is  rapid,  out  of  proportion  to  the  temperature,  at 
first  full  and  bounding,  later  small  and  compressible.  A  hemic 
murmur,  systolic  in  time,  is  sometimes  heard  over  the  pre- 
cordia,  not  transmitted.  Respiration  is  accelerated.  There  is 
often  sense  of  oppression  in  the  chest.     Dyspnea  may  be  a 


256  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

prominent  symptom,  due  to  anemia  or  to  edema  of  the  lungs. 
There  may  be,  especially  after  some  days  of  severe  illness, 
slight  dullness  and  diminished  respiratory  murmur  over  the 
dependent  portions  of  the  lung,  accompanied  by  slight  cough, 
resulting  from  hj^ostatic  congestion.  Cheyne-Stokes  respira- 
tion may  appear  toward  the  end.  Hiccough  is  present  in  a 
large  per  cent,  of  fatal  cases,  and  if  obstinate  is  always  to  be 
regarded  unfavorably.  Epistaxis  is  occasionally  seen.  The 
blood  pressure  is  low. 

Anemia  increases  with  intense  rapidity,  half  the  red  cells 
sometimes  being  destroyed  in  twenty-four  hours.  The  number 
usually  falls  to  one  to  two  million  during  the  attack.  Except 
for  the  absolute  diminution  of  the  fluid  portion  of  the  blood 
as  a  consequence  of  purging  and  vomiting,  the  number  of  red 
cells  per  cubic  millimeter  would  appear  much  smaller  than  it 
does.  It  is  occasionally  difficult  to  obtain  a  drop  for  ex- 
amination by  the  usual  method.  It  appears  relatively  thinner 
than  normal  and  the  cover-glass  may  adhere  to  the  oil  immersion 
objective  rather  than  to  the  slide.  On  coagulation  the  serum 
may  appear  yellow  (cholemia)  or  reddish  (hemoglobinemia), 
though  neither  is  constant.  Macrocytes,  microcytes,  poikilo- 
cytes,  shadows,  polychromatophiles,  and  basophiles  are  found, 
especially  during  convalescence.  The  color  index  shows 
nothing  characteristic;  it  may  be  normal  or  above,  at  first 
falling  gradually  until  convalescence  is  estabhshed.  The 
hemoglobin  per  cent,  usually  runs  parallel  with  the  red  cell 
count.  It  is  generally  reduced  to  25  to  50  per  cent.,  some- 
times lower,  as  in  a  case  of  Hoffmann^^  in  which  the  patient 
recovered  notwithstanding  a  fall  to  12  per  cent. 

In  one  of  my  fatal  cases  the  patient  was  practically  ex- 
sanguinated. He  had  been  treated  actively  with  enteroclysis 
and  hypodermoclysis  and  the  fluid  obtained  by  puncture  of 
the  lobe  of  the  ear  was  straw  colored.  The  cover-glass  ad- 
hered to  the  lens  rather  than  to  the  shde.  Only  a  few  very 
pale  red  cells  were  to  be  seen  in  each  field  of  the  microscope. 
The  lowest  hemoglobin  percentage  observed  in  a  case  recover- 
ing was  thirty.  It  is  often  asserted  that  during  pyrexia  there  is 
a  leucocytosis,  and  the  polymorphonuclears  are  increased  often 


BLACKWATEE    FEVER  257 

to  90  per  cent.  With  falling  temperature  there  is  a  pro- 
nounced large  mononuclear  increase  with  leukopenia.  How- 
ever, the  average  of  a  number  of  differential  counts  made  at 
irregular  intervals  during  the  attack  shows  a  marked  increase 
in  the  large  mononuclears,  a  decided  diminution  of  small 
mononuclears,  and  a  slight  increase  of  polymorphonuclears. 
Pigmented  leucocytes  are  common.  Christophers  and  Bent- 
jgyi65  iiave  made  interesting  observations  on  the  phagocytosis 
of  red  blood  corpuscles  in  the  spleen  of  a  case  of  blackwater 
fever.  In  a  differential  count  of  2,200  spleen  cells  1.7  per 
cent,  were  large  macrophages  containing  red  cells,  and  1.3 
per  cent,  were  small  mononuclear  cells  containing  red  blood- 
cells.  In  both  kinds  of  cells  were  seen  blood  corpuscles  show- 
ing no  evident  alterations,  corpuscles  more  or  less  decolorized, 
and  clear  vacuoles  about  the  size  of  red  blood-cells.  The 
closest  scrutiny  of  the  engulfed  cells  failed  to  reveal  the  pres- 
ence of  parasites  or  other  evidence  of  parasitic  invasion.  This 
extensive  phagocytosis  of  apparently  normal  cells  is  of  interest 
from  the  standpoint  of  pathogenesis.  The  platelets  are 
numerous  and  of  large  size.  The  alkalinity  of  the  blood  is 
often  diminished.  In  spite  of  the  destruction  of  red  cells  the 
specific  gravity  remains  relatively  high.  This  is  no  doubt  due 
to  the  quantity  of  material  in  solution  in  the  serum.  During 
convalescence  the  specific  gravity  falls.  Stephens  and  Chris- 
tophers"^ give  the  following  as  the  result  of  their  observation 
on  tonicity:  "In  blackwater  fever  there  is  occasionally  a 
remarkably  low  tonicity;  in  other  cases  it  has  the  normal 
value  or  somewhat  raised  value,  as  in  malaria.  The  low 
or  normal  value  in  blackwater  may  be  due,  as  we  have  pre- 
viously suggested,  to  the  fact  that  the  weak  corpuscles- — 
those  of  high  tonicity — are  destroyed;  or  it  may  be  due  to  th'e 
fact  that  the  tonicity  of  the  corpuscles  as  a  whole  is  changed 
after  the  liberation  of  hemoglobin."  The  presence  of  malarial 
parasites  has  been  dealt  with. 

Blackwater  fever  is  not  a  very  painful  affection,  but  the 
vomiting  and  thirst  make  the  patient  intensely  wretched. 
Besides  the  abdominal  pains  there  are  headache  and  aching  of 
the  back  and  limbs.     He  is  usually  terrified  at  the  appearance 


258  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

of  the  urine.  His  expression  is  one  of  anxiety  and  apprehension, 
and  a  fear  of  death  often  seizes  him.  He  is  restless  and  irri- 
table. In  children  especially  there  is  usually  tossing  of  the 
head  from  side  to  side.  Later  there  is  prostration,  intense 
languor,  perhaps  somnolence.  Formication  and  numbness 
in  the  hands  and  toes  are  'occasional  complaints.  Delirium, 
when  present,  is  usually  quiet.  When  suppression  ensues  the 
symptoms  may  be  typic  of  those  in  uremia,  but  this  is  not 
constant;  delirium  may  be  of  the  low,  muttering  variety; 
convulsions  are  often  missing,  and  the  mind  may  be  clear  until 
shortly  before  death,  when  coma  supervenes.  There  may  be 
involuntary  discharge  of  urine  and  feces. 

The  causes  of  death  are  three:  Suppression  of  urine,  ex- 
haustion, and  cardiac  paralysis.  In  my  fatal  cases  exhaustion 
has  been  the  commonest  mode  of  exit.  Suppression  some- 
times takes  place  when  the  urine  is  clearing  or  is  already  clear. 
Uremic  symptoms  do  not  result  from  suppression  in  black- 
water  fever  as  frequently  as  in  other  conditions.  This  is 
probably  due  to  two  causes:  first,  elimination  through  vomit- 
ing and  purging  is  free;  secondly,  metabolism  is  diminished  as 
a  result  of  deficient  oxygenation.  Exhaustion  is  usually  the 
result  of  the  tremendous  destruction  of  blood-cells,  together 
with  inability  of  the  hematopoietic  organs  to  meet  the  de- 
ficiency, or  to  pyrexia.  Occasionally  hiccough  plays  a  r61e  in 
exhaustion.  The  patient  may  die  early  with  symptoms  of 
shock  or  may  linger  several  days  in  a  typhoid  state.  Cardiac 
paralysis  is  usually  due  to  thrombosis  of  the  heart.  Plehn^ 
regards  this  as  a  common  cause  of  death.  Goltmann  and 
Krauss''-  have  shown  that  in  some  cases  of  death  from  syncope 
there  exists  a  marked  cardiac  nerve  degeneration  and  empty 
cylinders. 

It  would  manifestly  be  of  great  practical  importance  if  the 
symptoms  of  an  impending  attack  of  hemoglobinuria  could  be 
recognized.  This  is  possible,  if  at  all,  only  in  a  very  general 
way.  Plehn^^  says  that  an  onset  is  to  be  feared  when  the 
patient  has  lived  some  six  months  in  a  blackwater  fever  area 
and  has  had  malaria  at  short  intervals,  when  this  malaria  has 
been  treated  improperly  with  insufficient  quinine  dosage,  when 


BLACK  WATER    FEVER  259 

he  looks  downcast,  and  perhaps  shows  a  mild  icterus  of  the 
sclera  and  skin.  This  might,  however,  forebode  a  relapse  of 
ordinary  malaria.  Sometimes,  he  further  states,  there  occurs  a 
certain  depressed  condition,  a  characteristic  mental  apathy  with 
physical  restlessness,  phenomena  which  are  hard  to  describe, 
but  have  often  been  encountered  by  one  who  has  seen  many 
cases  develop.  Also  the  presence  of  albuminuria  should  cause 
suspicion  as  this  tends  to  be  absent  in  simple  tropic  fever, 
even  with  a  temperature  of  4i°C.  Koch^^  designates  as  "  black- 
water  fever  candidates"  those  in  whom  a  few  hours  after  taking 
quinine  the  temperature  mounts  to  38°C.  or  more,  the  urine 
becomes  decidedly  darker,  and  the  next  morning  a  mild  icterus 
is  evident.  Ziemann*^  has  frequently  observed  in  blackwater 
fever  candidates  the  following  blood  changes,  which,  however, 
are  not  constant: 

1.  The  more  frequent  appearance  of  decided  basophile  and 
polychromatophile  degeneration  of  the  red  cells. 

2.  The  rapid  solution  of  the  red  cells  in  a  salt  solution,  in 
which  normal  cells  do  not  dissolve. 

3.  A  decided  diminution  of  the  coagulability  of  the  blood. 
This  writer  also  regards  urobilinuria  as  a  valuable  prognostic 

sign. 

Relapses  are  not  infrequent  and  several  may  occur,  often 
befalling  the  patient  when  he  is  thought  to  be  doing  well. 
It  may  be  difficult  to  distinguish  relapses  from  recurrences. 
Convalescence  may  very  properly  be  regarded  as  the  dividing 
line,  those  occurring  during  convalescence  being  considered  as 
relapses  and  those  later  as  recurrences.  Plehn^^  believes  that 
recurrences  are  rare  unless  provoked  by  quinine.  Of  eighteen 
recurrences  recorded  by  Vedy*'  one  occurred  after  less  than 
three  months,  fourteen  from  three  to  six  months,  two  from  six 
to  twelve  months,  and  one  longer.  It  is  remarkable  that 
nine  recurrences  happened  just  three  months  from  the  date  of 
the  last  attack.  My  experience  has  been  that  in  persons  having 
more  than  one  attack  the  attacks  are  more  often  separated  by 
intervals  of  a  year  or  more. 

Complications  and  Sequelae. — These  are  singularly  few  in 
variety.     Nephritis  in  some  degree  is  an  almost  constant  com- 


26o  ENDEMIC   DISEASES    OF    THE    SOUTHERN    STATES 

plication,  and  may  cause  death  from  suppression  during  the 
attack.  It  may  heal  in  a  remarkably  short  time.  As  a  sequel 
it  is  not  infrequent  and  may  persist  for  days  or  weeks,  causing 
slow  and  incomplete  convalescence  or  death.  The  changes  in 
the  kidney  may  be  attributed  to  the  irritating  effect  of  hemo- 
globinuric  urine  and  to  the  pyrexia. 

In  sixteen  cases  I  have  been  able  to  make  examinations  of 
urine  at  periods  varying  from  a  few  days  to  fourteen  years  after 
the  last  attack.  In  eight  cases  the  examination  was  negative. 
The  others  may  be  noted  as  follows: 

F.  S.,  white,  male,  aet.  seventeen,  one  attack,  1899;  urinalysis, 
Feb.  27,  1907,  showed  a  trace  of  albumin,  no  casts,  no  symptoms 
of  nephritis. 

A.  J.,  white,  male,  aet.  eighteen,  two  attacks,  last  one  Oct., 
1904;  urinalysis,  Sept.  21,  1906,  showed  albumin  J^^  gram  liter, 
very  numerous  cylindroids  and  hyaline  casts,  moderate  number 
of  granular.     Anemia,  edema  of  lids  and  ankles. 

Mrs.  H.,  white,  female,  aet.  twenty-five,  one  attack  fourteen 
years  ago;  urinalysis,  Sept.  25,  1906,  showed  the  presence  of 
albumin  and  a  few  granular  casts.     No  symptoms. 

M.  C,  white,  female,  aet.  ten,  two  attacks,  last  one  Sept. 
24,  1906;  urinalysis,  on  Oct.  8,  1906,  showed  a  moderate 
amount  of  albumin,  no  casts.  Anemia,  edema  of  face  and 
ankles,  indigestion. 

E.  C,  white,  female,  aet.  seven,  five  attacks,  last  one  Nov. 
15,  1906;  urinalysis,  Dec.  4,  1906,  nitric  acid  test  for  albumin 
negative,  microscope  showed  a  very  few  cylindroids  and 
hyaline  and  granular  casts. 

R.  A.,  mulatto,  male,  aet.  forty-four,  one  attack  Nov.  13, 1905; 
urinalysis,  Aug.  22,  1906,  showed  no  albumin,  moderate  number 
of  cylindroids,  and  a  few  hylaine  casts. 

J.  P.,  white,  male,  aet.  thirty-seven,  several  attacks,  last  one 
Sept.  21,  1907;  urinalysis,  July  28,  1908,  a  slight  trace  of  albu- 
min, a  few  hyaline  casts,  very  few  granular. 

W.  S.,  male,  white,  aet.  forty- two,  one  attack,  which  oc- 
curred Feb.,  1905;  urinalysis,  June  27,  1908,  no  albumin,  a  few 
cylindroids. 

The    possibilities    of    the    abnormalities    of    urine    and    the 


BLACKWATER    FEVER  261 

symptoms  in  the  cases  being  produced  by  other  causes  than 
the  hemoglobinuria  should  be  borne  in  mind. 

Anemia  and  consequent  debility  and  digestive  disturbances 
are  not  uncommon.  Rare  complications  are:  paraplegia, 
tetanic  convulsions,  purpura  hemorrhagica,  dysentery,  pneu- 
monia, pancreatitis,  abscess  of  the  liver,  erysipelas,  parotiditis, 
retinal  hemorrhage,  pleurisy,  and  neuralgia.  I  have  seen 
tonsillitis  once  as  a  complication. 


CHAPTER  Xm 
DIAGNOSIS  OF  BLACKWATER  FEVER 

This  is  usually  made,  and  as  a  rule,  correctly  before  the 
physician  arrives.  The  history  of  malaria,  the  fever,  vomiting, 
jaundice,  and  blackwater  are  pathognomonic.  Though  the 
parasites  are  so  frequently  missed,  on  examination  of  the 
blood  there  is  usually  a  mononuclear  leucocytosis,  and  pig- 
mented leucocytes  may  be  found. 

The  diagnosis  from  paroxysmal  hemoglobinuria  might  pre- 
vent difficulties.  In  this  rare  condition  the  attacks  usually 
follow  chilling  of  some  portion  of  the  body,  and  the  attack  is 
usually  of  short  duration  and  seldom  fatal.  In  hemoglobinuric 
fever  there  is  given  a  history  of  several  years  of  residence  in 
an  endemic  region,  repeated  attacks  of  malaria,  with  often  the 
presence  of  parasites,  pigmented  leucocytes,  and  a  mononu- 
clear leucocytosis  in  the  blood. 

The  conditions  which  have  been  most  frequently  con- 
founded with  hemoglobinuric  fever  are  yellow  fever  and  bilious 
remittent  fever. 

In  localities  where  yellow  fever  and  blackwater  fever  prevail 
their  differentiation  is  not  easy.  The  following  are  the  chief 
points  of  difference: 

Hemoglobinuric  fever  Yellow  fever 

Endemic.  Epidemic. 

One  attaclc  predisposes.  One  attacli  confers  immunity. 

Occurs  usually  after  several  years  of  Attacks  also  newcomers, 
residence. 

Malarial  history  always  given.  May  be  no  history  of  malaria. 

Prodromata  common  Uncommon. 

Icterus  intense,  early,  always  present.  Icterus  usually  slight,  begins  on  third 

or  fourth  day;  may  be  absent. 

Conjunctiva  jaundiced.  Usually  congested  at  first. 

Hemoglobinuria.  Albuminuria  or  hematuria. 

Blood    may   show   malaria   parasites.  Absent, 
pigmented  leucocytes,  and  mononu- 
clear leucocytosis. 


BLACKWATER    FEVER  263 

Hemoglobinuric  fever  Yellow  fever 

Bilious  vomiting.  Vomit  clear  or  black. 

Hemorrhages  uncommon.  Relatively  common. 

Spleen  usually  much  enlarged.  Enlargement  slight. 

Increasing  pulse.  Pulse     retards     with     stationary     or 

increasing  temperature  (Faget's  sign). 
Albuminuria  from  beginning.  Usually  appears  from  second  to  fourth 

day. 

A  rather  striking  coincidence  is  the  relative  immunity  of 
the  negro  to  both  diseases. 

Certain  cases  of  bilious  remittent  fever  present  points  of 
striking  similarity.  This  is  well  illustrated  by  the  following 
case  which  was  presented  to  me  by  the  messenger  and  by  the 
family  on  my  arrival  as  one  of  "hematuria:" 

A.  H.,  white,  male,  aged  thirty-nine,  timberman,  lived  in 
a  malarial  country  eighteen  years.  Never  had  hemoglobinuric 
fever.  He  had  been  having  chills  at  intervals  all  summer 
and  fall,  slight  fever,  "dumb  chills,"  and  slight  jaundice  for 
three  weeks,  no  quinine  for  two  months;  badly  salivated  from 
seven  large  doses  of  calomel  taken  several  days  ago.  Ex- 
amination Nov.  29,  1906,  four  and  a  half  hours  after  first  pas- 
sage of  "bloody  water."  Temperature  99^5;  pulse,  92;  marked 
jaundice  of  skin  and  sclera;  has  been  vomiting;  liver  region 
tender;  spleen  extends  to  anterior-superior  spinous  process 
and  to  within  ij^  inches  of  the  umbiUcus.  Blood  examina- 
tion showed  two  large  pigmented,  intracorpuscular  parasites, 
hemoglobin  65  per  cent.  Urine  "port  wine"  color,  acid  1.014; 
nitric  acid  test  for  albumin  negative,  biliary  coloring  matter 
abundant,  no  hemoglobin.  Microscopic  examination  negative. 
Under  quinine  treatment  the  urine  cleared  in  thirty-six  hours 
and  the  fever  left  in  a  few  days,  going  no  higher  than  loi}^. 
The  anemia  and  enlarged  spleen  were  yet  present  when  I 
last  saw  the  patient,  two  weeks  after  the  attack. 

The  following  scheme  will  help  to  differentiate  hemoglobinuric 
fever  and  bilious  remittent  fever: 

Hemoglobinuric  fever  Bilious  remittent  fever 

Onset  sudden.  Onset  slower. 

Jaundice     develops    rapidly    and  be-     Jaundice   develops  more  slowly  and  is 

comes  intense.  not  so  intense. 

Parasites  frequently  absent.  Parasites  usually  present. 


264  ENDEMIC   DISEASES    OF   THE    SOUTHERN   STATES 

Hetnoglobinuric  fever  Bilicnis  remittent  fever 

Albuminuria  constant.  Albuminuria  not  constant. 

Urine   colored  by   hemoglobin  or   its     Urine  colored  by  bile, 
derivatives. 

The  differential  diagnosis,  as  attempted  by  some  writers, 
from  'quinine  poisoning  in  malarial  subjects"  is  futile  and 
impossible,  as  this  condition  is  a  mode  of  hemoglobinuric 
fever. 


CHAPTER  XIV 
PROGNOSIS  OF  BLACKWATER  FEVER 

The  prognosis  of  hemoglobinuric  fever  is  grave,  and  should 
be  "guarded  and  Delphic."  Probably  the  most  valuable 
prognostic  sign  is  the  quantity  of  urine;  the  chemic  analysis 
and  microscopic  examination  are  not  of  great  value  in  prognosis. 
Anuria,  the  most  dreaded  symptom,  is  to  be  feared  if  the  daily 
quantity  of  urine  falls  below  200  c.c.  If  suppression  super- 
venes the  outlook  is  extremely  serious  and  is  unfavorable  in 
proportion  to  early  onset.  When  a  patient  is  tided  over  a 
period  of  suppression,  as  occasionally  happens,  he  usually 
dies  during  convalescence  of  exhaustion,  subsequent  nephritis, 
or  embohsm.  The  phenolsulphonephthalein  test  should  be 
used  as  the  index  to  kidney  efficiency. 

Excessive  and  uncontrollable  vomiting  is  a  bad  omen, 
exhausting  the  sufferer  and  interfering  with  nutrition  and 
medication.  Diarrhea  is  probably  in  many  cases,  with  suppres- 
sion or  a  tendency  thereto,  a  Hfe-saving  measure,  and  may 
be  particularly  responsible  for  the  relative  rarity  of  uremic 
symptoms  under  these  circumstances.  Singultus  is  present  in 
a  majority  of  fatal  cases,  and  when  obstinate  is  always  un- 
favorable. Remittent  or  intermittent  temperature  is  usually 
favorable.  Somnolence,  with  diminishing  amount  of  urine; 
coma,  especially  of  early  onset;  petechiae,  epistaxis  or  other 
hemorrhage  an4  algor  forebode  evil. 

Thrombus  formation  in  the  heart  or  large  vessels  may  cause 
sudden  death  when  the  patient  is  thought  to  be  progressing 
favorably.  Plehn^  believes  that  loud  heart  murmurs  accom- 
panied with  weak,  irregular  pulse  denote  heart  thrombus. 
This  condition  is  almost  certainly  fatal,  usually  in  five  to  eight 
days. 

The  larger  the  share  partaken  by  quinine  in  the  etiology 
of  the  indi\adual  case  the  better  the  prognosis,  provided  the 
case  is  not  further  aggravated  by  quinine. 
26s 


266 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


Cases  occurring  in  victims  of  malarial  cachexia  or  of  com- 
plications are  usually  more  serious. 

The  mortality  varies  unaccountably  from  year  to  year, 
some  seasons  evincing  a  series  of  mild  cases,  others  an  appall- 
ing mortality.  In  a  certain  parish  of  Louisiana  in  1867  many 
cases  are  said  to  have  occurred,  of  which  not  less  than  95  per 
cent,  died.^^^  Fisch,^  who  placed  the  mortality  on  the  Gold 
Coast  at  20  per  cent.,  states  that  until  two  or  three  decades 
previous  nearly  all  who  were  attacked  died.  On  the  other 
hand.  Banks'*  makes  the  well-nigh  incredible  statement 
Treated  with  Quinine,  2107  Cases,  538  Deaths,  23.5  Per  Cent. 


Number  of  deaths 


Vieth' ,. 

Dryepondt' 

Mense'°* 

Powell"!^ 

Gelpeiis 

Diesingi"^ 

Haggei"5 

Schellong'"* 

Reynolds"* 

Doering" 

Hanley^* 

Mofiati" 

Gorgas"" 

Steudel'^ 

Malone'" 

Brem'* 

Coste'" 

Steggall'" 

Woldert"* 

Otto" 

Schlayer'' 

Austin!" 

Herrick'* 

Curry''" 

Burot  andLegrand' 

Cardamatis'^ 

Broden'" 

Theophanidis"^. . . 
Oeconomou"'. . .  .  . 

McDanieU" 

Berenger-Feraud'*' 


9 

7 

3 

3 

2 

3 

7 

2 

7 

3 

I 

I 

6 

13 

3 

9 

2 

20 

3 

18 

3 

120 

14 

14 

3 

IS 

7 

3 
S 

I 

8 

I 

I 

3 

I 

i>3S2 

354 

12 

7 

23 

14 

18 

S 

8S 

3S 

286 

66 

BLACKWATER    FEVER  267 

Treated  without  Quinine,  1183  Cases,  123  Deaths,  10.4  Per  Cent. 


Number  of 


Tomaselli"" 

Navarre' 

Henric"' 

Kohlstocki" 

Koch" 

Hopkins"^ 

Bertrand"" 

OUwig=" 

Wittrock'^ 

Ziemann'' 

A.  Plehn^ 

Kleine'*  

Krauss'"* 

McElroy84 

Goltman  and  Krauss''^ 

Malone'" 

Costei" 

Hearsey^" 

Seal>3» 

Ruge"2 

Dryepondt  and  Vancampenhouf 

Howard" 

Ketchen"! 

Masterman'* .  . 

Herrick*' 

Curry'"" 

Cardamatis'-^ 

Ensor'*" 

Brodeni" 

Pancot"" 

Theophanidis"* 

Oeconomou"" 

McDanieli" 

F.  Plehn^ 

Cardamatis"^' 

Woldert^s 

Alexandropoulos'^' 


456 

II 

25 

7 

9 

31 

93 

25 

IIS 


Number  of  deaths 


268 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


Treatment  Mixed  or  not  Recorded,  3815  Cases,  779  Deaths,  20.4 
Per  Cent. 


Number  of  cases 


nber  of  deaths 


Kanellis"'' 

Poole' 

Rothschuh' 

GuioP 

Gouzien^'^ 

Meixner^' 

Hofft=3 

Wendland^' 

Daniels'' 

Wellman'n 

Ipscher""! 

Kruger" 

Simon'" 

Kerr  Cross^" 

Osborn^*' 

O'Neill^' 

Burns" 

Shropshire'^' 

DempwolS'^'^ 

Lipari'" 

Gouducheau'^' •  . 

Cochran'** 

Kelsch  and  Kiener'* 

Bolton" 

Grail™ 

Forde"* 

Grenet'" 

Rousseau"^ 

Carmouze"' 

Mericourt"* 

Koryllos'" 

Pampoukis"* 

Cardamatis"* 

Parathyris"^ 

Prout'"' 

Jacobs'" 

DeCruz'** 

DeBlasi'«« 

Orme'»« 

Thompstone'" 

Canal  Zone  Reports'*' 

Hearsey '*' 

Baker'" 

Langley'*'' 

Will'** 

Fagan'** 

Deaderick'* 

Skeleton'*" 

German  Protectorate  Reports'*' 


S6 


i8s 
S3 


17 

27 

10 

5° 

16 

177 

17 

19 

IS 

642 

109 

17s 

113 


158 
35 


22 

6 

30 

9 

22 

3 

28 

5 

156 

35 

30 

6 

23 

3 

24 

8 

147 

16 

13 

6 

3 

27 

S 

423 

73 

14 

3 

7 

2 

27 

4 

lOI 

15 

538 


BLACKWATER    FEVER  269 

that  he  treated  over  loo  cases  in  the  Congo  State  without  a 
death. 

Pampoukis^^  gives  the  mortality  of  blackwater  fever  as 
6.6  per  cent.;  Crosse^  20  per  cent.;  Kanellis*  22.4  per  cent.; 
Berenger-Feraud*-  23.1  per  cent.;  Barthelemy-Benoit^-  25 
per  cent.;  Bertrand^""  25  per  cent.;  Carre^  27  per  cent.;  Man- 
son^^  25  per  cent.;  Cassan^'  32.1  per  cent.;  MicheP^^  ^;i  to 
50  per  cent.;  Schellong^  42  per  cent.;  Reynolds^  50  per  cent.; 
Scott^  60  per  cent. 

The  following  Hst  of  7105  cases,  with  1440  deaths,  shows  a 
mortality  of  20.2  per  cent.  It  is  compiled  from  various 
sources.  The  first  column  of  figures  shows  the  number  of 
cases,  the  second  the  number  of  deaths. 

F.  Plehn^  asserts  that  mortality  is  highest  in  first  attacks, 
but  the  following  table  of  Daniels-^  does  not  bear  him  out: 

Of  136  first  attacks 31  or  22. 7  per  cent,  were  fatal. 

Of  33  second  attacks 8  or  24.0  per  cent,  were  fatal. 

Of  IS  third  or  fourth  attacks  .    2  or  13.3  per  cent,  were  fatal. 


CHAPTER  XV 
PROPHYLAXIS  OF  BLACKWATER  FEVER 

A.  Plehn  has  shown  that  hemoglobinuric  fever  is  preventable 
to  a  greater  degree  even  than  malaria.  In  1897-99  among 
the  officers  of  Cameroon  who  used  no  prophylaxis  there  oc- 
curred in  578  months  of  residence  287  cases  of  malaria  and  31 
of  blackwater  fever,  or  i  malaria  case  for  every  2  months 
and  I  of  blackwater  for  each  18.5  months.  Ten  per  cent, 
of  the  blackwater  cases  terminated  fatally.  During  the  same 
period  among  those  who  used  prophylaxis  there  were  in  446 
months  of  residence  90  cases  of  malaria  and  6  of  hemo- 
globinuric fever,  or  i  case  of  malaria  for  each  5  months 
of  residence  and  i  of  hemoglobinuric  fever  for  each  74 
months,  none  of  which  were  fatal.  Thus,  while  malaria 
was  reduced  by  half,  the  morbidity  of  blackwater  fever  was 
lowered  to  one-fourth.  The  lowered  mortality  of  these  cases 
is  even  still  more  remarkable;  similar  results  were  observed  by 
Moffatt.^'*  Even  Koch^^  beheves  that  through  appropriate 
quinine  prophylaxis  not  only  malaria  but  blackwater  fever, 
in  an  overwhelming  majority  of  instances,  can  be  exterminated. 

The  prophylaxis  of  hemoglobinuric  fever  consists  of  the 
prophylaxis  and  proper  treatment  of  malaria.  There  are 
two  chief  methods  in  vogue  for  the  use  of  quinine  as  a  pre- 
ventive of  hemoglobinuric  fever:  Plehn's  method,  Y2  gram  every 
fifth  evening,  and  Koch's,  i  gram  on  two  successive  days  of 
each  week. 

The  results  of  A.  Plehn,  recorded  above,  were  obtained 
with  i^-gram  prophylaxis,  but  Ruge*^  maintains  that  better 
consequences  follow  Koch's  method,  and  gives  the  following 
figures:  According  to  the  1903  statistics  of  Cameroon,  there 
were  among  those  who  used  quinine  regularly  12  cases  of 
blackwater  fever,  of  which  8  employed  the  Plehn  method; 
3  first  Plehn's,  then  Koch's;  and  only  i  Koch's  method 
270 


BLACKWATER    FEVER  271 

regularly.  Of  35  cases  among  irregular  users,  17  employed  the 
i2-gram  method  and  only  3  the  i-gram  method.  From 
these  figures  it  is  evident  that  Koch's  method  is  preferable 
even  when  not  systematically  employed. 

It  is  necessary  to  persist  in  prophylaxis  not  only  while  in 
the  blackwater  fever  district,  but  for  several  months  thereafter. 
As  a  majority  of  the  first  cases  occur  from  the  second  to  the 
fourth  year  of  residence,  it  is  evident  that  greater  care  should 
be  exerted  during  this  period. 


CHAPTER  XVI 
TREATMENT  OF  BLACKWATER  FEVER 

The  discussion  of  the  treatment  of  hemoglobinuric  fever  has 
probably  been  productive  of  more  harsh  and  prejudiced  con- 
troversies than  has  any  other  question  in  therapeutics.  The 
bone  of  contention  is  quinine. 

It  is  unnecessary  to  review  the  discussions  or  to  rehearse 
the  arguments  for  or  against  the  etiologic  relation  of  quinine 
to  blackwater  fever.  No  vaHd  conclusion  can  be  reached 
except  through  results  of  a  large  series  of  cases  treated  with 
and  without  quinine.  The  collection  recorded  under  Prog- 
nosis shows  a  mortality  of  25.5  per  cent,  in  cases  treated  with 
quinine,  and  10.4  per  cent,  in  cases  in  which  no  quinine  was 
used.  This  number  of  cases  probably  eliminates  all  errors 
and  should  be  convincing.  \Vhile  the  results  of  the  series 
prove  that  the  mortality  is  higher  under  the  routine  treatment 
with  quinine,  they  should  not  be  taken  to  exclude  absolutely 
the  use  of  quinine  in  some  cases  of  hemoglobinuric  fever, 
for  under  certain  circumstances  quinine  may  be  of  value.  It 
is  difi&cult — in  fact,  sometimes  impossible — to  say  whether 
quinine  is  indicated  or  contra-indicated  in  a  certain  case. 

Mannaberg*-  gives  the  following  general  rules  to  aid  in  a 
decision: 

1.  When,  without  quinine  preceding,  hemoglobinuria  occurs 
and  the  blood  examination  shows  the  presence  of  malarial 
infection,  quinine  is  undoubtedly  to  be  exhibited. 

2.  When  the  hemoglobinuria  occurs  after  one  dose  of  quinine, 
while  the  anamnesis  shows  that  the  patient  previously  took 
quinine  without  bad  effect,  and  the  parasites  are  present  in 
the  blood,  quinine  is  also  to  be  exhibited.  If  a  paroxysm  of 
hemoglobinuria  should  follow  within  a  few  hours,  the  repeti- 
tion of  the  drug  should  be  made  dependent  upon  whether  or 
not  the  parasites  have  in  great  part  disappeared.     In  the  for- 


BLACKWATER    FEVER  273 

mer  case  the  quinine  may  be  stopped,  at  least  for  a  time. 
But  if  the  blood  examinations  show  that  the  parasites  have 
increased  in  number  the  quinine  is  to  be  continued. 

3.  When  anamnesis  shows  that  the  patient  suffered  previ- 
ously from  hemoglobinuria  following  quinine  and  the  blood 
examination  is  negative,  quinine  is  to  be  absolutely  avoided. 

4.  When  the  case  manifests  a  severe  malarial  infection 
(numerous  parasites  on  examination)  and  at  the  same  time  an 
assured  intolerance  to  quinine  in  the  shape  of  hemoglobinuria, 
the  decision  is  very  difficult. 

Marchiafava  and  Bignami^^  believe  that  the  only  guide  in- 
dicating to  the  physician  whether  to  give  or  to  withhold 
quinine  ought  to  be  the  result  of  a  blood  examination. 

Bastianelli's'^^  canon  is  as  follows: 

1.  If  a  hemoglobinuria  occurs  during  a  malarial  paroxysm 
and  the  parasites  are  found  in  the  blood,  quinine  should  be 
given. 

2.  If  parasites  are  not  found  in  the  blood,  quinine  should 
not  be  given. 

3.  If  quinine  has  already  been  given  before  the  hemoglo- 
binuria has  appeared  and  no  parasites  are  found,  its  use  should 
be  suspended;  but  if  parasites  persist  it  should  be  continued. 

Thayer'-^''  states  his  rules,  modified  from  BastianelH,  thus: 

1.  If  the  attack  occurs  spontaneously  with  a  malarial 
paroxysm,  the  blood  showing  the  presence  of  parasites,  quinine 
should  be  freely  administered  hypodermically  or  intravenously. 

2.  If  the  parasites  have  disappeared,  either  as  a  result  of 
the  paroxysm  itself  or  of  doses  of  quinine  already  given,  it 
may  be  as  well  to  abstain,  at  least  for  a  time,  from  the  adminis- 
tration of  the  drug.  It  cannot  ameliorate  the  further  course 
of  the  paroxysm,  and  the  possibility,  if  it  has  been  already  given, 
that  the  symptoms  may  be  in  part  due  to  quinine  may  be 
thought  of. 

3.  If  an  attack  arise  in  the  middle  of  an  ordinary  malarial 
infection,  after  taking  quinine,  it  is  best  to  abstain,  for  a  time, 
at  any  rate,  from  the  further  use  of  the  drug.  That  which 
has  been  given  may  have  been  enough  to  control  the  affection. 

4.  If,  however,  in  an  attack  coming  on  after  quinine,  the 


274  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

parasites  continue  to  develop,  quinine  should  be  again  adminis- 
tered, despite  the  slight  possibility  of  its  injurious  action. 
The  dangers  from  the  further  development  of  the  parasites  are 
probably  the  greater. 

5.  In  post-malarial  hemoglobinuria  quinine  is,  of  course, 
useless. 

The  following  rules  of  Vedy^^  are  practical: 

1.  If  Uving  parasites  (not  merely  evidence  of  their  former 
existence,  pigment)  are  detected  twenty-four  hours  after  the 
beginning  of  the  attack  80  centigrams  of  a  salt  of  quinine  may 
be  injected  subcutaneously. 

2.  If  the  parasites  are  not  visible  do  not  administer  quinine. 

3.  If  in  doubt,  that  is  to  say  if  the  microscopic  examination 
of  the  blood  cannot  be  made,  do  not  give  quinine. 

It  may  be  seen  that  the  authorities  quoted  lay  great  stress 
on  the  presence  of  the  parasites  as  a  guide  to  the  administration 
of  quinine.  I,  however,  cannot  agree  with  those  who  hold  that 
quinine  should  be  exhibited  in  every  case  where  the  microscopic 
examination  shows  the  presence  of  parasites.  It  has  been 
shown  conclusively  that  parasites  are  present  in  a  very  large 
proportion  of  cases  examined  early.  It  has  also  been  shown 
that  in  an  equally  large  number  of  cases  the  parasites  disappear 
spontaneously.  In  these  cases  quinine  is,  to  say  the  least, 
superfluous. 

In  my  opinion,  the  only  conditions  in  which  quinine  is 
indicated  are:  first,  where  the  parasites  show  no  tendency 
to  disappear  after  forty-eight  hours  from  onset;  second,  in 
the  infrequent  cases  of  intermittent  hemoglobinuria  where  the 
outbreak  corresponds  with  parasitic  sporulation. 

If  it  is  decided  to  give  quinine,  it  should  be  injected,  in 
dilute  solution,  into  the  muscles  as  directed  for  the  treatment 
of  pernicious  malaria.  Given  by  the  mouth  it  upsets  the  stom- 
ach and  may  not  be  absorbed. 

Even  in  cases  of  mildest  onset  the  patient  should  be  con- 
fined to  bed  from  the  start,  and  should  be  kept  quiet,  either 
by  persuasion  or  by  sedatives.  Sudden  death  on  slight  exer- 
tion sometimes  occurs.  The  patient  should  not  be  trans- 
ported from  one  place  to  another;  the  Plehn  brothers  observed 


BLACKWATER    FEVER  275 

anuria  as  a  frequent  consequence  of  moving  patients  from  place 
to  place.  Chilling  of  the  body,  especially  when  the  tem- 
perature is  low,  should  be  carefully  avoided.  When  vomiting 
is  not  a  prominent  feature,  liquid  nourishment  may  be  given 
freely;  buttermilk  and  albumen  water  are  the  most  suitable. 
Sweet  milk  is  often  ejected  as  a  thick  curd,  molded  ropy  by 
the  esophagus  in  the  act  of  vomiting.  Animal  broths,  barley 
and  oatmeal  water,  lemonade,  and  orange  juice  are  allowable. 
Rectal  alimentation  is  unsatisfactory. 

There  is  ao  specific.  Methylene-Uue  has  proved  disappoint- 
ing. Besides  being  a  renal  irritant,  it  masks  the  color  of  the 
urine,  a  most  serious  objection.  Salicylic  acid  probably  has 
no  effect  further  than  to  upset  the  stomach  and  increase  the 
discomfort.  With  the  false  idea  that  a  hemorrhage  has  to 
be  checked,  gallic  and  tannic  acids,  ergot,  and  similar  drugs 
are  frequently  given;  these  cannot  possibly  be  of  any  benefit. 
Carbolic  acid  and  other  renal  irritants  should  not  be  used. 

The  bowels  should  move  early  and  often,  and  calomel  pos- 
sesses advantages  over  other  purgatives;  it  is  more  easily 
retained,  is  a  bland  diuretic,  and  is  the  best  of  intestinal  anti- 
septics. Two  large  doses  are  usually  advised;  3  to  5  grains 
are,  as  a  rule,  sufficient,  repeated  pro  re  nata. 

Quennec's^^^  chloroform  treatment  has  been  successful  in  some 
hands.  The  originator  claims  for  the  method  three  points 
of  value: 

1.  Controls  vomiting. 

2.  Increases  output  of  urine. 

3.  Diminishes  albuminuria. 

He  treated  more  than  fifty  cases  with  no  mortality.  The 
following  is  his  formula:  Chloroform,  6  grams;  gum  arabic,  8 
grams;  sweetened  water,  250  grams.  This  amount  is  used 
daily,  a  sip  taken  every  ten  minutes.  In  addition,  Quennec 
used  quinine  i  gram  daily  subcutaneously,  and  sulphate  of 
soda  and  senna  by  rectum.  The  excessive  administration  of 
chloroform  might  be  harmful,  as  it  is  a  cardiac  depressant, 
renal  irritant,  and  lowers  the  blood  pressure. 

Cardamatis^-  gives  ether  in  every  case  of  hemoglobinuric 
fever.     In  ordinary  cases  he  prescribes  a  teaspoonful  in  sweet- 


276  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

ened  water  every  three  hours,  and  increases  the  dose  if  the 
urine  diminishes  in  quantity.  In  cases  of  suppression  he 
gives  as  much  as  a  teaspoonful  every  hour,  at  the  same  time 
injecting  hypodermically  i  c.c.  every  two  or  three  hours.  He 
maintains  that  by  this  means  the  pulse  is  strengthened,  pre- 
cordial anxiety,  dyspnea,  and  vomiting  are  relieved,  and  a 
profuse  diuresis  is  provoked. 

I  have  had  no  experience  with  ether  in  the  treatment  of 
blackwater  fever,  but  would  consider  it  too  irritating  to  the 
kidneys  for  general  use. 

Hearsey^^"  used  with  good  results  a  modification  of  Stern- 
berg's yellow  fever  treatment.  The  original  Sternberg  formula 
is:  sodium  bicarbonate,  150  grains;  mercury  perchloride  J^ 
grain;  water,  2  pints.  Sig.:  i^^  ounces  every  hour.  Hearsey 
gives  sodium  bicarbonate,  10  grains;  liquor  hydrargyri  per- 
chloride, 30  minims,  every  two  or  three  hours. 

A  method  of  treatment  recently  introduced  and  extrav- 
agantly extolled  by  its  originator  is  that  of  Vincent.^'*  This 
writer  maintains  that  calcium  chloride  is  not  only  a  pre- 
ventive, but  has  extraordinary  curative  powers.  During  the 
attack  from  4  to  6  grams  are  given  daily  by  the  mouth,  or  from 
I  to  2  grams  dissolved  in  normal  salt  solution  hypodermically. 
He  asserts  that  it  acts  as  an  antihemolysin,  and  that  in  persons 
in  whom  an  attack  of  blackwater  fever  may  be  provoked 
at  will,  by  a  dose  of  quinine,  the  previous  administration 
of  calcium  chloride  will  forestall  the  outbreak.  It  is  worthy 
of  mention  that  this  drug  has  been  used  successfully  in  parox- 
ysmal hemoglobinuria  by  Saundby,  and  in  hemophilia  by 
Wright  and  others. 

I  have  employed  calcium  in  six  cases,  of  which  three  ended 
fatally.  The  series  is  too  small  to  permit  of  very  definite 
conclusions  as  to  results  of  treatment,  but  it  would  appear 
that  the  results  claimed  by  Vincent  were  not  obtained.  The 
three  fatal  cases  were  in  persons  whose  health  was  probably 
not  more  undermined  from  previous  attacks  of  malaria  or  other 
causes  than  the  average  patient  who  is  attacked  with  hemo- 
globinuric  fever.  It  is  worthy  of  note  that  the  cause  of  death 
in  these   three   cases  was  not  syncope  nor  suppression,   but 


BLACKWATER    FEVER  277 

exhaustion  due  directly  to  hemolysis,  the  very  process  which 
calcium  chloride  was  used  to  combat.  No  treatment  other 
than  supportive  was  used  which  might  modify  the  antihemo- 
lytic  effects  of  the  calcium  chloride. 

Hyposulphite  of  soda,  introduced  into  the  treatment  of  ma- 
laria by  Polli'^^  in  1867,  has  been  used  extensively  in  the 
treatment  of  hemoglobinuria.  Its  use  is  probably  not  attended 
with  any  signal  results.  O'Sullivan-Beare^'^  used  with  good  re- 
sults a  decoction  of  the  root  of  cassia  beareana,  a  native  plant. 
Gouzien  employed  an  infusion  of  the  leaves  of  cassia  occidentalis. 

Teas  made  from  the  leaves  of  folia  combreti  alti  and  of  aphloia 
theaeformis  are  also  highly  recommended.-' 

The  fever  does  not  usually  run  sufficiently  high  to  call  for 
treatment.  The  coal-tar  preparations  should  be  assiduously 
avoided.  Cold  baths  may  be  productive  of  harm  by  increasing 
the  blood  destruction,  but  the  hyperpyrexial  cases  sponging 
with  tepid  water  may  be  resorted  to. 

Vomiting,  if  not  intense,  is  often  benefited  by  a  mustard 
plaster  on  the  epigastrium.  The  fly-blister  formerly  used 
should  be  abandoned.  Draughts  of  hot  water  or  carbonated 
water  sometimes  assist  in  relieving  this  troublesome  symptom. 
Cracked  ice  may  be  tried.  Morphine  hypodermically  should 
be  given  unhesitatingly  when  other  measures  fail.  Any  evil 
effects  are  more  than  outweighed  by  its  enabling  the  stomach 
to  retain  liquids. 

An  important  measure  toward  the  prevention  and  relief  of 
nausea  and  vomiting  is  to  maintain  the  recumbent  position. 
Medicine,  water,  and  nourishment  should  be  taken  through  a 
drinking  tube  or  the  ordinary  invalid's  cup,  and  the  bed  pan 
or  urinal  should  be  used  when  evacuating  the  bowels  or 
bladder. 

It  is  imperative  to  allay  the  restlessness  often  present  in  these 
cases.  For  this  purpose  chloral  and  bromide  of  soda  by  rectum, 
morphine  hypodermically,  or  sulphonal  or  small  doses  of 
chloroform  by  mouth  are  useful. 

Probably  the  most  important  indication  in  the  treatment  is 
the  prevention  of  suppression.  Medicinal  diuretics  usually  do 
harm.  One,  turpentine,  widely  used  in  some  sections,  should 
be. condemned  in  the  strongest  terms.     It  is  one  of  the  most 


278  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

violent  renal  irritants,  and  in  some  persons  small  doses  may 
cause  suppression  or  hematuria.  Water  is  the  best  diuretic, 
and  as  much  should  be  given  by  mouth  as  can  be  retained. 
Lewis,  *^  of  North  Carolina,  was  the  first  to  recommend  the  use 
of  normal  salt  solution  by  hypodermoclysis  and  by  the  rectum 
in  the  treatment  of  hemoglobinuric  fever,  though  Laveran^' 
attributes  the  priority  to  Gouzien.  The  latter  recommends 
the  daily  injection  of  100  to  300  grams  of  a  ?xo  per  cent, 
solution,  in  conjunction  with  the  rectal  injection  of  200  grams 
four  to  six  times  in  twenty-four  hours.  The  use  of  salt 
solution  is  the  very  best  means  of  combating  and  treating 
anuria.  It  is  probably  better  to  use  a  hypertonic  solution. 
In  mild  cases  where  the  urine  is  free  the  rectal  use  is  usually 
sufficient,  but  in  cases  where  suppression  threatens  or  is  im- 
minent the  solution  should  be  given  subcutaneously  or  in- 
travenously and  in  larger  quantities  and  oftener  than  advised 
by  Gouzien.  Mild  counter-irritation  over  the  region  of  the 
kidneys  may  be  tried. 

Werner^"  in  1902,  suggested  nephrotomy  for  anuria.  Such 
an  operation  has  been  recorded  in  only  three  instances.  Zie- 
mann^^  mentions  a  case  in  a  young  female  patient  in  whom 
suppression  had  existed  two  days.  The  capsule  of  the  right 
kidney  was  split  and  peeled  off  to  the  hilum  and  nephrotomy 
performed  through  the  convexity  of  the  organ.  The  operation 
was  well  borne,  and  subsequently  200  c.c.  of  cloudy,  albuminous 
urine  was  voided  from  the  bladder.  During  the  following  days 
complete  suppression  recurred,  and  the  patient  died. 

In  Kruger's^^^  case  decortication  of  one  kidney  was  done  five 
days  after  the  onset  of  anuria,  and,  although  the  secretion  of 
urine  was  profusely  reestablished,  the  patient  died  of  progressive 
weakness. 

Kulz^^'  reports  a  case  in  a  man  during  his  second  attack. 
Three  and  a  half  days  after  the  onset  of  anuria  nephrotomy 
upon  one  kidney  was  performed  through  Simon's  incision. 
Vomiting,  which  was  formerly  uncontrollable,  ceased  im- 
mediately. Three  hours  after  the  operation  30  c.c.  of  blood 
were  voided  from  the  bladder.  In  eight  hours  the  dressing  was 
saturated  with  bloody  icteric  urine,  which  necessitated  changing 


BLACKWATER    FEVER  279 

the  dressing  every  three  hours.  Twenty-four  hours  after  the 
operation  the  patient  died.  Though  a  microscopic  examination 
of  the  kidney  could  not  be  made,  upon  gross  inspection  the 
nephrotomized  kidney  appeared  much  more  nearly  normal 
than  the  other. 

Supportive  measures  are  essential.  Alcohol  in  all  its  forms 
is  inadmissible.  Strychnine  is  useful,  and  should  be  given  hypo- 
dermically  when  circumstances  permit.  Digitalis  has  proved 
serviceable  in  my  hands.  Doering^^  had  good  effects  from  stro- 
phanthus.  The  aromatic  spirits  of  ammonia  and  hypodermic 
injections  of  ether  have  been  recommended.  Transfusion  of 
blood  has  been  used,  it  is  said,  with  excellent  results.  The  elder 
Plehn^"  says  that  he  had  four  attacks,  in  which  Kohlstock 
treated  him  with  inhalations  of  oxygen,  and  that  nothing  else 
did  him  so  much  good.  Unfortunately  this  method  of  treat- 
ment is  not  often  possible  in  private  practice. 

The  after-treatment  should  have  a  care  for  the  diet,  which 
should  be  non-nitrogenous  and  consist  largely  of  liquids  at 
first.  A  tonic  of  organic  iron  is  indicated,  and  digestive  dis- 
orders when  present  should  receive  appropriate  treatment. 

A  question  of  practical  importance  is,  how  soon  after  the 
attack  to  begin  the  administration  of  quinine.  A  dose  given 
too  early  might  possibly,  in  some  persons,  precipitate  hemolysis. 
On  the  other  hand,  delay  may  permit  an  outbreak  of  malaria 
accompanied  by  hemoglobinuria.  Upon  the  ground  that  most 
of  the  sensitive  cells  have  succumbed  during  the  attack  and 
that  the  newly  formed  cells  are  probably  more  susceptible  than 
those  that  have  withstood  the  attack,  I  am  of  the  opinion 
that  quinine  should  be  begun,  carefully  at  first,  a  short  time 
after  the  attack  has  subsided  and  before  blood  regeneration  is 
fairly  established.  One  grain  of  quinine  three  times  daily, 
increased  gradually  every  other  day,  is  a  safe  procedure.  If 
the  temperature  rises  or  the  urine  becomes  distinctly  darker  no 
further  attempt  to  increase  the  dose  should  be  made. 

In  the  present  state  of  our  knowledge  it  is  probably  Utopian 
to  discuss  the  treatment  of  hemoglobinuric  fever  by  anti- 
hemolytic  sera,  but  such  has  been  successfully  accomplished 
by  Widal  and  Rostaine  in  paroxysmal  hemoglobinuria. 


PELLAGRA 

CHAPTER  XVn 
INTRODUCTION 

Pellagra  is  an  endemic  disease,  the  cause  of  which  is  at  the 
present  time  unknown,  is  usually  of  slow  progress,  and  charac- 
terized by  more  or  less  seasonal  periodicity,  and  by  lesions  of 
the  skin,  alimentary  tract  and  nervous  system,  terminating  in 
recovery,  cachexia,  insanity  or  death. 

The  list  of  names  by  which  the  disease  is  known  is  a  long  one, 
the  chief  of  which  are  Alpine  scurvy,  dermotagra,  Asturian 
leprosy,  Asturian  rose,  disease  of  the  Landes,  Italian  leprosy, 
maidismus,  corn  bread  disease,  sun  disease,  elephantiasis 
italica,  psychoneurosis  maidica,  mal  de  rosa,  mal  del  sole,  mal 
de  misere,  etc. 

History. — Our  history  of  pellagra  begins  in  Spain.  It  was 
first  observed  in  the  province  of  Oviedo  by  Caspar  Casal  who 
in  1735  wrote  a  treatise  in  which  he  described  it,  which,  however, 
was  not  printed  until  1762.  He  called  the  disease  mal  de  rosa. 
In  1787  Townsend  in  his  description  of  his  travels  through 
Spain  refers  to  his  observation  of  the  disease  in  Oviedo  and 
definitely  states  that  the  subjects  ate  little  meat  and  largely 
of  corn  and  other  vegetable  foods.  Corn  is  said  to  have  been 
introduced  into  Spain  between  1680  and  1700.  Oviedo  remains 
to  this  day  a  hot  bed  of  the  disease. 

Pellagra  was,  according  to  Terzagli,  known  in  Italy  even 
earlier  than  1730,  isolated  cases  having  been  observed  in  the 
neighborhood  of  Sesto  Calende.  The  disease  appears  to  have 
spread  rapidly  appearing  simultaneously  in  the  districts  of 
Milan,  Brescia,  Bergono,  and  Lodi  and  soon  after  in  the  vicinity 
of  Como,  Cremona,  Mantna  and  Paira,  toward  the  end  of  the 
century  extending  almost  entirely  throughout  Lombardy.  The 
name  Pellagra  was  given  the  malady  by  Prapolli  in  1771,  and 


282  ENDEMIC   DISEASES    OF   THE    SOUTHERN    STATES 

probably  means  "rough  skin."  As  the  disease  invaded  new 
areas  in  Italy  the  number  of  cases  in  the  earlier  foci  increased 
rapidly.  In  1 784  a  pellagra  hospital  was  established  in  Legnano 
under  the  supervision  of  the  elder  Strambio.  Marzari  in  1810 
is  said  to  have  been  the  first  to  infer  an  etiologic  relationship 


deitqnxnV. 
\CCJiCetacartKnaan 


Fig.  66. — Casal's  illustration  of  the  cutaneous  lesions  in  pellagra. 

between  the  consumption  of  maize  and  pellagra.  On  account 
of  the  early  invasion  of  Italy,  of  the  extensive  prevalence  of 
the  disease  in  that  country  and  of  the  attention  paid  to  the 
scourge  by  scientists  and  by  the  government,  Italy  may  well 
be  regarded  as  the  home  of  the  disease. 


PELLAGRA  283 

Our  first  knowledge  of  pellagra  in  France  originates  with 
Hameau  who,  in  1829,  published  his  observations  of  cases  since 
1818  in  the  vicinity  of  Teste-de-Buche  and  in  the  plain  of 
Arcachon  and  in  the  coast  region  of  the  Giroude.  For  the  last 
quarter  of  a  century  there  has  been  little  if  any  pellagra  in 
France. 

Pellagra  was  first  described  in  Roumania  by  Caillat  in  1854, 
who  states  that  the  disease  was  unknown  there  prior  to  1846. 
In  Corpi  isolated  cases  were  observed  in  1839,  but  only  since 
1856  has  the  malady  assumed  an  endemic  character.  Nicholas 
and  Hambon  reported  cases  in  Austria  near  Vienna  in  1794 
and  in  1846  an  epidemic  occurred  in  Roumania.  It  is  stated 
that  pellagra  was  observed  in  Great  Britain  in  i860. 

In  Africa  pellagra  was  first  described  by  Prumer  in  Egypt 
in  1847.  The  disease  was  practically  ignored  until  1893 
when  Sandwith  found  it  to  be  prevalent  in  patients  he  was 
treating  for  anchylostomiasis. 

In  the  United  States  the  definite  history  of  pellagra  goes 
back  to  1864  when  a  case  was  reported  by  Dr.  John  Gray  of 
Utica,  New  York,  and  another  by  Dr.  Tyler  of  Somersville, 
Massachusetts.  Both  patients  were  insane.  Shewell  of  Brook- 
lyn reported  a  case  of  pellagra  in  1883  in  an  Italian  sailor. 
Bemis  of  New  Orleans,  in  1889,  left  a  written  diagnosis  of  a 
case  in  a  white  female  in  the  Charity  Hospital. 

Babcock-^"  has  adduced  very  strong  evidence  in  favor  of 
the  existence  of  pellagra  in  the  South  Carolina  State  Hospital 
from  its  opening  in  1828.  A  case  history  which  he  reproduces 
in  full  from  the  records  of  the  institution  is  certainly  very  con- 
vincing.    This  case  was  admitted  in  1834. 

It  is  believed  that  the  terrific  mortality  among  the  prisoners 
in  the  Confederate  prison  at  Andersonville,  Georgia,  was  due 
in  part  to  pellagra.  The  medical  records  of  the  Civil  War, 
however,  do  not  conclusively  support  this  theory. 

Harris,-*' Atlanta,  in  1902,  reported  a  case  of  ankylostomiasis 
in  an  individual  presenting  all  the  typical  symptoms  of  pellagra. 
The  patient  was  a  native  of  Georgia  and  had  always  resided 
there.  It  is  worth  noting  that  both  Sandwith  and  Harris 
discovered  the  disease  in  the  investigation  of  uncinariasis. 


284  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

The  report  of  Harris  does  not  seem  to  have  excited  any 
terest  and  it  was  not  until  1907  that  the  disease  was  next 


ported,  this  time  by  Searcy^*-  as  an  epidemic  at  the  asylum  in 
Mt.     Vernon,    Alabama.     Reports    of    cases    then    followed 


PELLAGRA  285 

rapidly.  MerrilP^'  reported  a  case  in  Texas  in  i907;Babcock 
and  Watson^^^  in  South  Carolina  in  1908;  Bellamy-^''  in  North 
Carolina  in  1908;  Card-*^  in  Mississippi  in  1908;  Williamson-" 
in  Arkansas  in  1909;  Hewit-^^  in  Virginia  in  1909;  Pollock-*^ 
in  Illinois  in  1909  and  King^^°  in  Tennessee  in  1909.  Thayer-^^ 
is  said  to  have  observed  cases  in  Maryland  in  1905  and  1909. 

Geographic  Distribution. — The  distribution  of  pellagra  is 
peculiar.  In  Europe  it  is  found  in  Italy,  Roumania,  Austria, 
Hungary,  France,  Northern  Portugal,  Northern  Spain,  Bessa- 
rabia, Poland,  Kherson,  the  Island  of  Corfu,  Bosnia,  Herze- 
govina, Servia,  Bulgaria,  Turkey,  Greece,  England,  Scotland, 
Ireland,  Wales  and  the  Shetlands. 

In  Asia  it  has  been  found  in  Asia  Minor,  Persia,  Straits 
Settlements  and  in  North  Behar,  India. 

In  Africa  it  is  encountered  in  Lower  Egypt,  less  in  Upper 
Egypt,  in  the  coastal  regions  of  the  Red  Sea,  in  Algeria,  Tunis, 
Nyassa  and  Rhodesia,  South  Africa  and  Robben  Island. 

Pellagra  has  been  found  in  New  Caledonia,  Hawaii,  Cuba, 
Porto  Rico,  Barbadoes  and  Jamaica. 

In  South  America  it  has  been  reported  from  Brazil,  Argentina 
and  the  Columbian  Republic. 

Numerous  cases  are  recorded  in  the  Canal  Zone  and  the 
disease  is  found  in  Mexico. 

In  the  United  States  there  is  no  other  disease  known  to  be 
so  widely  disseminated  so  soon  after  its  recognition,  pellagra 
being  found  in  thirty-nine  states  including  the  District  of  Co- 
lumbia. The  most  intense  foci  of  infection  are  in  Virginia, 
North  Carolina,  South  Carolina,  Georgia,  Florida,  Kentucky, 
Tennessee,  Alabama,  Mississippi,  Arkansas,  Louisiana,  and 
Texas.  The  disease  is  frequent  in  part  of  Illinois;  pellagra 
is  found  sporadically  in  Maine,  Vermont,  Massachusetts, 
Connecticut,  Rhode  Island,  New  York,  New  Jersey,  Penn- 
sylvania, Maryland,  District  of  Columbia,  West  Virginia, 
Kansas,  Wisconsin,  Oklahoma,  Ohio,  Indiana,  Iowa,  Missouri, 
Michigan,  Minnesota,  Colorado,  New  Mexico,  Arizona,  Wash- 
ington, Oregon  and  California. 

Prevalence. — As  pellagra  is  not  a  reportable  disease  except 
in  a  small  portion  of  the  country  in  which  it  is  endemic,  accu- 


286  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

rate  statistics  of  its  prevalence  are  not  available.  In  19 12 
]vj;jgg305  estimated  that  there  were  between  6,000  and  10,000 
cases  in  the  United  States.  Roberts'""  believed  that  there  had 
been  at  least  30,000  cases  in  the  United  States  between  the 
years  1907  and  191 2. 

Basing  our  opinion  from  personal  observation  on  the  increas- 
ing prevalence  of  the  disease  in  Arkansas  and  upon  the  pub- 
lished reports  from  other  localities  we  believe  that  there  are 
at  least  25,000  cases  of  pellagra  in  the  United  States  at  this 
time  (August  i,  1915). 


CHAPTER  XVIII 
ETIOLOGY  OF  PELLAGRA 

Season. — Pellagra  is  subject  to  decided  seasonal  variations. 
In  the  United  States  the  months  of  most  frequent  occurrence 
are  from  March  to  July,  particularly  April,  May  and  June. 

The  following  table  is  compiled  from  cases  reported  in  the 
United  States  and  shows  the  occurrence  of  the  disease  by 
months. 


January. , . 
February. . 
March. .  .  . 

April 

May 

June 

July 

August .  . . . 
September 
October. .  . 
November 
December. 


57 
3° 
13 
18 


Most  of  the  cases  seen  by  one  of  us  in  eastern  Arkansas  came 
for  consultation  for  the  first  time  in  May  and  June,  while  of 
ninety-one  cases  seen  by  one  of  us  in  the  Arkansas  State  Hos- 
pital for  Nervous  Diseases,  the  admissions  for  pellagra  by 
months  were  as  follows: 


January 12 

February 3 

March 2 

April 4 

May II 

June 6 


July 7 

August 8 

September 9 

October 10 

November 12 

December 7 


By  an  analysis  of  115  cases  the  Thompson-McFadden  Pellagra 

Commission^^^  have  shown  that  there  is  no  particularly  marked 

287 


288  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

tendency  for  the  seasonal  recurrences  to  reappear  during  the 
same  month  year  after  year.  Relapses  may  occur  during  the 
fall  months  of  the  same  year  in  which  the  onset  appears. 

The  onset  appears  earlier  in  countries  lying  farther  south. 
In  Florida,  more  cases  originate  in  the  early  spring  months  than 
in  states  farther  north.  In  Italy  the  majority  of  first  cases  are 
said  to  occur  from  the  middle  of  March  to  the  middle  of  May 
and  the  disease  appears  somewhat  earlier  in  the  central  prov- 
inces than  in  the  northern  ones.  Sandwith^""  states  that  in 
examining  300  patients  in  Egypt  two-thirds  of  them  stated  that 
their  skin  lesions  were  first  seen  during  the  months  of  January 
and  February. 

Rainfall. — The  Thomson-McFadden  Commission^^^  observed 
that  if  during  the  spring  precipitation  is  high,  the  temperature 
low,  and  the  number  of  rainy  days  excessive  the  appearance  of 
acute  symptoms,  more  particularly  those  involving  the  brain, 
is  delayed. 

Altitude  and  Topography. — In  the  United  States  pellagra 
is  found  in  mountainous  regions,  as  in  southeastern  Kentucky 
and  northwestern  Georgia,  in  rolling  upland  regions  and  in 
lowland  and  swampy  regions.  In  the  eastern  hemisphere  also 
pellagra  occurs  from  the  Tyrolean  Alps  to  the  delta  of  the 
Nile.  In  Europe  the  disease  is  especially  prevalent  about  the 
lower  slopes  and  foothills  of  mountainous  regions. 

Sambon-'^  has  emphasized  the  frequency  with  which  pellagra 
cases  are  found  on  the  narrower  valleys  of  hilly  and  wooded 
country  trenched  by  swift-running  streams.  His  observations 
were  conducted  in  northern  and  central  Italy.  In  Kentucky, 
Georgia  and  South  Carolina,  Grimm^^^  classified  323  cases 
with  reference  to  the  distance  from  water  courses  with  the 
following  results: 

0  to    s°  ya-rds 31 

50  to  100  yards 35 

100  to  200  yards 49 

200  to  500  yards 118 

500  to      I  mile 51 

1  to      3  miles 10 

Exact  distance  not  determined 29 


PELLAGRA 


The  Tennessee  Pellagra  Commission^''  record  their  observa- 
tions with  reference  to  proximity  to  creeks  as  follows: 

Yes 78 

Not  observed 141 

No g  7 

Wood's-'^  experience  in  North  Carolina  was  similar  to  that 
of  Sambon  in  Italy. 

On  the  other  hand,  the  Thomson-McFadden  Commission^'^ 
investigated  conditions  on  a  large  island  off  the  coast  of  South 
Carolina,  the  distinguishing  feature  of  which  was  the  absence 
of  streams.  Pellagra  was  found  to  be  endemic  here.  In- 
vestigations were  also  undertaken  in  the  Panhandle  of  Texas 
where  the  rainfall  is  very  slight  and  running  streams  remarkably 
scarce.     Pellagra  cases  were  found  originating  here. 

The  most  that  can  be  said  regarding  the  relation  of  altitude 
and  topography  to  pellagra  is  that  it  seems  to  be  restricted  to 
certain  areas  which  vary  widely  in  these  characteristics. 

Race.— Generally  speaking  pellagra  is  commoner  in  the  white 
race  than  in  the  negro  as  shown  in  the  table  below: 


j        White 

Colored 

9,881 

a6 
298 

680 

46 

1,223 

74 

4,048 
6 

Roberts""" 

24 
18 

Albright-"". 

Randolph  and  Green^'" 

6 

Siler,  Garrison  and  McNeaP™ 

Tucker^"-* 

9 

203 

17 

Ark.  State  Hospital 

Total 

12,266 

4,431 

Siler,  Garrison  and  McNeaP'*  believe  that  this  ratio  is  not 
necessarily  indicative  of  a  relative  racial  resistance  to  pellagra 
in  negroes  but  rather  as  the  end-results  of  the  influence  of 
several  factors,  prominent  among  which  are  the  poor  hygienic 
conditions  under  which  the  people  live  in  villages  as  compared 
with  the  relative  isolation  of  the  bulk  of  the  colored  population 
on  farms. 
19 


290 


ENDEMIC   DISEASES    OF    THE    SOUTHERN    STATES 


There  are  undoubtedly  areas  in  which  the  disease  is  far  com- 
moner in  negroes  than  in  whites.  This  was  the  experience  of 
one  of  us  in  the  lowlands  of  eastern  Arkansas  where  many  cases 
were  seen  in  negroes  and  only  few  in  whites.  It  is  true  that 
relatively  few  white  persons  live  in  the  rural  districts  of  that 
particular  locality. 

As  recently  shown  by  Wolff^"^  pellagra  is  an  exceedingly  rare 
disease  among  Jews. 

Sex. — Foreign  observers  have  failed  to  note  any  significant 
influence  of  sex  on  the  prevalence  of  pellagra.  In  the  United 
States,  however,  and  particularly  in  the  South,  the  disease  is 
known  to  occur  with  a  notable  preponderance  among  females. 
Sixty-five  per  cent,  of  Niles^°°  cases  and  81  per  cent,  of  Low- 
gj.y'g306  -^ere  in  females.  At  least  two-thirds  of  the  eastern 
Arkansas  cases  seen  by  one  of  us  and  73  per  cent,  of  the  cases 
in  the  Arkansas  State  Hospital  were  in  females. 

A  compilation  of  cases  from  numerous  sources  shows  that 
females  are  affected  about  two  and  a  half  times  more  frequently 
than  males: 


Clark=i>2 

Harrington-'' 

MizelP" 

Siler  and  Nichols^*^ 

Thomson-McFadden  Commission 

BealP"^ 

Tucker^M 

Grimm-'- , 

Lavender 

Thomson-McFadden  Commission 

Albright"' 

Roberts^" 

Thompson 


Canal  Zone 

Rhode  Island 

Maryland 

Illinois 

South  Carolina 

Texas 

Virginia 

Kentucky,         South 

Carolina 

United  States 

South  Carolina 

Tennessee 

United  States 

Arkansas 


The  sex  distribution  of  the  cases  investigated  by  the  Thomson- 
McFadden  Commission  is  interesting,  i.  The  rate  of  preva- 
lence among  children  under  10  years  of  age  and  among  adults 


PELLAGRA  29I 

aged  45  years  and  older  is  practically  equal  in  the  two  sexes. 
2.  The  rate  of  prevalence  drops  among  males  between  the  ages 
of  19  and  45  years,  whereas  for  females  there  is  a  remarkable 
excess  of  prevalence  between  these  ages.  3.  In  both  males  and 
females  there  is  a  striking  fall  in  prevalence  between  the  ages 
of  10  and  20  years. 

Age. — No  period  of  life  is  free  from  the  attack  of  this  disease. 
It  has  been  found  in  infants  at  the  breast  and  in  the  centenarian. 
The  youngest  pellagrin  of  which  we  can  find  a  report  is 
one  mentioned  by  Haase.'"^  which  was  but  4  weeks  old. 
He  also  speaks  of  two  others  respectively  6  and  8  weeks 
of  age.  The  age  of  the  oldest  pellagrin  on  record  is  102 
years,  that  being  the  age  of  a  pellagrous  woman  reported  by 
Roberts.""" 

These  extremes  of  age,  however,  are  rare.  The  youngest 
pellagrin  we  have  seen  was  a  child  of  2,  while  the  oldest  was 
69.  The  following  table  shows  the  ages  of  the  91  cases  seen 
by  one  of  us  in  the  Arkansas  State  Hospital  for  Nervous 
Diseases: 

Between  11  and  20  years 2  cases. 

Between  21  and  30  years 19  cases. 

Between  31  and  40  years 28  cases. 

Between  51  and  60  years 11  cases. 

Above  60  years 7  cases. 

Lavinder^"^  found  532  cases  in  children  under  5  years  of  age, 
2,192  cases  between  the  ages  of  5  and  20  years,  9,404  between 
20  and  40,  and  5,309  cases  in  individuals  over  40  years  old. 

Merck's'^""  table  of  ages  shows  that  the  greatest  number  of 
cases  occur  between  the  ages  of  40  and  50  years,  and  the  smallest 
number  of  cases  under  5  years. 

From    o  to    5  years 46  cases  or    0.9  per  cent. 

From    5  to  15  years 406  cases  or    8.3  per  cent. 

From  15  to  30  years 715  cases  or  14.  7  per  cent. 

From  30  to  40  years 919  cases  or  19.0  per  cent. 

From  40  to  50  years i)Or7  cases  or  21.0  per  cent. 

From  50  to  60  years 868  cases  or  18.  7  per  cent. 

From  60  to  70  years 638  cases  or  13 .  i  per  cent. 

Over  70  years 228  cases  or    4.6  per  cent. 

4,836  100.3  per  cent. 


292 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


Heredity. — The  role  of  heredity  in  pellagra  has  been  a  moot 
question  for  many  years,  and  is  one  that  in  all  probability  will 
not  be  settled  until  the  etiologic  factor  of  the  disease  is  dis- 
covered. Some  investigators  contend  that  pellagra  is  truly 
hereditary,  that  it  may  be  transmitted  from  parent  to  child, 
but  there  is  little  or  no  evidence  to  prove  that  such  is  the  case. 
No  instance  of  pellagra  has  been  reported  in  the  new-born  and 
as  stated  above  the  youngest  case  on  record  was  in  a  child  of 
four  weeks  of  age. 

On  the  other  hand,  the  majority  of  investigators  contend  that 
pellagra  is  not  hereditary  in  the  sense  that  syphilis  is,  but 
that  pellagra  in  the  parents  predisposes  the  children  to  the 
disease. 

Civil  Condition. — While  it  would  seem  from  our  present 
knowledge  of  pellagra  that  the  civil  condition  of  an  individual 
could  have  little  or  nothing  to  do  with  him  contracting  the 
disease,  it  will  be  seen  from  the  accompanying  table  that 
pellagra  is  much  more  prevalent  among  the  married  than 
those  of  any  other  civil  condition. 


Grim=== 

Tucker=»< 

Roberts^" 

Albright^"' 

Thomson 

and 
McFadden 

Arkansas 

state 
Hospital 

Total 

Married 

208 

37 

42 

204 

150 

S3 

698 

Single 

83 

14 

12 

92 

25 

20 

246 

Widowed.... 

32 

4 

5 

20 

9 

18 

88 

Divorced. . .  . 

0 

0 

I 

0 

0 

0 

I 

323 

55 

60 

316 

184 

91 

1,033 

Occupation. — It  has  long  been  considered  in  Italy  that 
pellagra  is  found  almost  exclusively  among  farmers  or  field 
laborers,  and  that  "peasant  life,  poverty  and  polenta"  are  the 
three  p's  responsible  for  this  disease.  While  it  is  undoubtedly 
true  that  the  majority  of  the  pellagrins  of  Italy  are  of  the  farmer 
class,  this  does  not  seem  to  be  the  case  in  America.  According 
to  the  Thompson-McFadden  Pellagra  Commission, ^^^  the  most 
significant  fact  concerning  occupation  brought  out  by  their 
investigation  is  the  prevalence  of  the  disease  among  housewives. 
They  state,  however,  that  this  means  httle  more  than  that 


PELLAGRA  293 

pellagra  is  most  prevalent  among  women  of  the  age  at  which 
they  are  usually  employed  in  the  house. 

Social  Condition. — As  stated  above,  poverty  has  long  been 
considered  as  one  of  the  prime  causes  .of  pellagra,  and  the 
studies  of  numerous  investigators  show  that  while  pellagra  may 
attack  those  of  affluent  circumstances  it  is  much  more  preva- 
lent among  the  poor. 

Thus  the  Thompson-McFadden  Pellagra  Commission^'^  re- 
port as  follows: 

Cases  living  in  squalor 2 

Cases  living  in  poverty 28 

Cases  living  where  only  the  necessities  of  life  were  obtained  200 

Cases  living  in  comfort 41 

Cases  living  in  affluence 6 

277 

Lavinder,'"'*  in  a  study  of  16,960  cases  of  pellagra,  found  8,491 
were  poor,  6,970  were  of  moderate  means,  and  only  1,499  were 
well-to-do. 

Hygiene. — That  the  hygienic  surroundings  of  an  individual 
may  play  an  important  role  in  the  etiology  of  pellagra  seems  at 
least  possible. 

Grimm-^-  found  that  of  296  cases  11  lived  under  good  sanitary 
conditions  in  the  home,  36  under  fair  conditions,  while  249 
cases  came  from  homes  where  the  sanitary  conditions  were  bad. 

Marie^"*  states,  however,  that  lack  of  cleanliness  in  the  home 
is  not  a  cause,  as  many  peasants  keep  their  houses  neat. 

Siler,  Garrison  and  McNeal-"^  consider  inefficient  methods 
of  the  disposal  of  human  excreta  a  material  factor  of  the 
epidemiology  of  pellagra  in  those  sections  where  the  disease  is 
endemic.  In  Spartanburg  County,  S.  C.,  they  found  pellagra 
endemic  in  all  of  the  mill  villages,  and  in  all  they  found  un- 
screened surface  or  pail  privies.  In  two  mill  villages  of  other 
counties  where  every  house  contained  a  water-carriage  flush 
closet  they  failed  to  find  a  single  case  of  pellagra  which  had 
certainly  originated  in  these  villages.  In  the  city  of  Spartan- 
burg these  investigators  observed  that  the  active  foci  of  the 
disease  were  found  in  the  portions  of  the  city  where  unscreened 
pail  and  surface  privies  were  used.     They  found  that  230  cases 


294  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

of  the  241  observed  in  the  city  came  from  homes  where  the 
above-named  privies  were  used,  and  several  of  the  remaining 
eleven  cases,  while  using  the  water-carriage  system  themselves, 
lived  in  communities  where  unscreened  surface  privies  were 
common,  and  some  of  them  used  by  pellagrins. 

Rural  and  Urban  Dwellers.- — Aside  from  the  tilling  of  the  soil 
it  has  been  alleged  that  the  mere  fact  of  dwelling  in  rural  dis- 
tricts predisposes  to  pellagra.  Practically  all  writers  on  Italian 
pellagra  are  agreed  upon  this  point,  and  Roberts^""  writing  of 
conditions  in  general,  including  America,  states  that  this  is  a 
disease  of  rural  districts,  that  "pellagra  stops  at  the  city 
gates." 

This  statement  is  not  in  accord  with  the  findings  of  most 
observers  in  the  United  States.  The  Thompson-McFadden 
Pellagra  Commission-^"  found  the  disease  much  more  prevalent 
in  the  congested  districts  of  the  mill  villages  than  in  either  the 
urban  or  rural  districts.  This  coincides  with  the  findings  of 
Grimm,-''  who  observed  more  pellagra  among  dwellers  of  towns 
than  among  city  or  country  residents. 

Of  the  17,763  cases  reported  by  Lavinder^"*  5,212  were  city 
dwellers,  784  lived  in  towns,  while  11,767  were  inhabitants  of 
rural  districts. 

In  Arkansas,  however,  the  inhabitants  of  even  the  largest 
cities  have  easy  access  to  the  country  and  most  of  such  make 
visits  of  more  or  less  extent  to  rural  districts.  This  statement 
is  true  also  of  a  great  deal  of  the  pellagrous  area  of  this  country, 
and  we  have  never  seen  a  city  pellagrin  who  has  not  made 
visits  to  the  country. 

Other  Predisposing  Causes. — Among  the  other  factors 
which  seem  to  be  predisposing  causes  of  pellagra  the  incidence 
or  previous  occurrence  of  other  diseases  is  important.  However, 
the  occurrence  of  disease  in  childhood  does  not  seem  to  predis- 
pose the  adult  to  pellagra. 

Alcoholism  appears  to  play  an  important  role  in  predisposing 
the  individual  to  this  chsease,  while  many  pellagrins  are  found 
to  have  indulged  in  venereal  excesses.  Pregnancy  and  fre- 
quent child  bearing  may  account  for  the  development  of  the 
disease  in  some  cases.     One  case  in  this  connection  which  has 


PELLAGRA  295 

been  under  treatment  by  one  of  us  for  some  time  is  of  more 
than  ordinary  interest  as  it  followed  pregnancy  and  puerperal 
convulsions. 

Malaria  and  hook-worm  are  frequent  concomitant  diseases 
with  pellagra,  the  former  having  been  seen  by  us  in  several 
cases. 

It  seems  to  us  that  the  factor  to  be  considered  in  this  connec- 
tion is  not  that  the  previous  or  concomitant  disease  per  se 
predisposes  the  individual  to  pellagra,  but  that  by  lowering  his 
vitality  and  power  of  resistance  it  renders  him  more  prone  to 
contract  it. 

Theories  of  Etiology. — There  are  two  theories  as  to  the 
etiology  of  pellagra:  (i)  that  it  is  due  to  some  dietetic  error; 
and  (2)  that  it  is  an  infectious  disease,  caused  by  some  as  yet 
unknown  parasite. 

It  might  be  well  to  mention  here,  not  because  it  has  any 
scientific  bearing  upon  the  subject  of  the  etiology  of  pellagra, 
but  for  historic  interest,  that  there  are  certain  French  pella- 
grographers  who  contend  that  pellagra  is  not  a  disease  entity, 
but  that  it  is  a  symptom-complex  which  may  develop  in  any 
cachectic  state.  Outside  of  a  small  group  of  writers  this 
theory  has  received  scant  attention. 

Dietetic  Dyscrasia. — From  the  earliest  description  of  pellagra 
by  Casal  down  to  the  present  time  Indian  corn  or  maize  has 
been  incriminated  in  connection  with  the  etiology  of  the  dis- 
ease. However,  Casal  and  his  contemporaries,  some  of  whom 
in  all  probability  independently  thought  of  corn  as  the  cause  of 
pellagra,  did  not  formulate  their  views  on  the  subject  and  only 
in  a  vague  indefinite  sort  of  way  laid  the  malady  at  the  door  of 
maize.  Pellagra  was  a  new  disease — at  least  it  had  only  newly 
been  observed — and  Indian  corn  was  a  new  product,  so  it  was 
rather  natural  that  the  physician  of  the  times  should  connect 
the  two. 

It  was  not  until  1810,  however,  that  any  definite  theory  as 
to  the  manner  in  which  corn  caused  pellagra  was  formulated. 
At  this  time  Marzari  propounded  his  theory  that  the  disease 
was  due  to  a  lack  of  certain  nutritive  elements  in  the  corn, 
and  almost  immediately  there  sprang  up  two  schools  of  thought: 


296  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

the  zeists  (from  Za  Mays),  who  supported  the  corn  theory, 
and  the  anti-zeists,  who  discredited  it.  However,  it  was  not 
long  before  the  zeists  became  divided  among  themselves  and 
many  new  theories  were  formulated  as  to  the  exact  manner  in 
which  corn  caused  this  disease. 

The  following  list  comprises  the  principal  theories  as  to  the 
manner  in  which  corn  acts  as  an  etiologic  factor  in  the 
production  of  pellagra: 

1.  Lack  of  nutritive  elements. 

2.  Toxicity  of  normal  corn  itself. 

3.  Toxicity  of  corn  due  to  germination  process. 

4.  Toxicity  of  corn  due  to  products  elaborated  by  the  action 
of  certain  microorganisms. 

5.  Toxicity  of  corn  due  to  products  produced  in  the  ali- 
mentary tract  after  ingestion. 

6.  Toxicity  of  corn  due  to  poisonous  substances  in  the  grain 
which  act  only  after  being  sensitized  by  the  rays  of  the  sun. 

7.  Action  of  certain  parasites  of  corn  ingested  with  that 
grain. 

The  first  and  second  of  these  theories  have  been  thoroughly 
disproven  by  the  many  careful  analyses  of  corn  which  show 
that  this  grain  is  rich  in  nutritive  value,  containing  a  large 
percentage  of  fat  and  nitrogenous  substances,  and  is  readily 
assimilated  by  the  body.  Further,  it  has  been  shown  that 
pellagra  is  often  found  in  well-nourished  persons,  thus  proving 
that  it  is  not  a  disease  due  to  lack  of  nutritive  elements;  and 
finally,  there  are  many  districts  in  which  corn  has  been  very 
extensively  used  as  an  article  of  diet  for  long  periods  of  time  in 
which  pellagra  has  never  been  found. 

The  third  theory,  that  pellagra  is  due  to  a  toxin  elaborated 
during  the  process  of  the  germination  of  the  corn,  has  also 
been  shown  to  be  untenable  by  the  above-mentioned  facts, 
and  even  the  most  ardent  zeists  have  abandoned  these 
theories. 

The  fourth  theory,  the  so-called  toxico-chemical  theory,  that 
pellagra  is  due  to  toxins  produced  in  corn  by  the  action  of 
certain  microorganisms,  has  probably  had  the  widest  vogue  of 
any  theory  as  to  the  etiology  of  this  disease.     It  was  to  the 


PELLAGRA  297 

elaboration  and  promulgation  of  this  theory  that  the  great 
Lombroso  gave  the  last  twenty-five  years  of  his  life. 

A  great  many  microorganisms,  moulds  and  bacteria  have 
been  described  by  investigators  in  this  field,  but  even  Lom- 
broso, himself,  was  unable  to  incriminate  any  one  of  them. 

The  most  frequent  parasite  of  spoiled  corn  is  the  Penicillium 
glaucum  or  common  blue  mould.  This  organism  penetrates 
into  the  interior  of  the  corn  and  has  been  thought  by  many 
to  produce  the  specific  toxin  of  pellagra. 

Other  microorganisms,  which  have  been  described  and 
defined  as  the  cause  of  the  toxin  of  pellagra,  are  Sporisorium 
maidis,  Eurotium  Herbariorum,  Aspergillus  glauciis,  Oidium 
lactis  maidis,  misentericus  vulgaris,  bacterium  thermo,  etc. 

Numerous  chemical  studies  of  spoiled  corn  have  been  made 
and  several  substances  have  been  isolated,  the  chief  of  which, 
according  to  Marie, ^"^  are  the  so-called  red  oil,  pellagrosine,  and 
a  resinous  substance. 

With  these  substances  and  with  the  spoiled  corn  itself  Lom- 
broso conducted  many  experiments  in  animals,  especially  in 
dogs  and  chickens,  and  considered  that  he  had  produced  a 
true  pellagra  in  them. 

So  firmly  convinced  were  the  Italian  people  that  Lombroso 
was  correct  in  his  contentions  that  they  instituted  the  most 
elaborate  measures  calculated  to  prevent  the  use  of  spoiled 
corn  as  food  and  thus  act  as  a  prophylaxis  to  the  disease. 

De  Giaxa^"^  considered  that  pellagra  was  due  to  a  toxic 
substance  elaborated  in  the  intestinal  tract  by  the  action  of 
the  colon  bacillus  on  ingested  corn.  He  considered  that  the 
properties .  of  the  organisms  were  changed  by  growth  with  the 
corn,  and  alleged  to  have  produced  a  toxic  substance  from  the 
growth  of  this  bacillus  on  a  corn  culture  media.  Another 
auto-intoxication  theory,  advanced  by  Neusser,""  was  that  a 
toxin  was  produced  in  the  alimentary  tract  from  a  so-called 
"receptive  mother  substance"  which  was  the  product  of  the 
action  of  the  Bacillus  Maydis  on  corn. 

The  so-called  photodynamic  theory  of  the  etiology  of  pellagra 
was  advanced  by  Ravbitschek^"  and  others.  They  maintained 
that  all  corn  contains  a  certain  toxic  substance  which,  after 


298  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

ingestion  of  the  corn,  is  taken  up  by  the  blood  stream  where  it 
remains  inactive  until  it  becomes  sensitized  by  the  action  of 
the  sun's  rays  on  the  exposed  portion  of  the  body. 

Next  to  the  toxico-chemical  theory  so  strongly  defended  by 
Lombroso  and  his  followers  the  idea  that  pellagra  is  due  to  a 
specific  microorganism,  either  mould  or  bacteria  ingested  with 
corn,  has  probably  been  the  most  popular. 

The  organisms  which  have  been  described  and  incriminated 
in  this  respect  are  legion  and  only  a  few  of  them  will  be  men- 
tioned. The  ordinary  blue  mould,  Penicillium  glaucum,  has 
probably  been  accused  in  this  respect  by  more  investigators 
than  any  of  the  other  parasites  of  corn. 

Cini'^-  contended  that  pellagra  was  an  aspergillosis  due  to 
two  moulds,  Aspergillus  fumigatus  and  Aspergillus  fiaverscens. 

Tizzoni"^  described  a  specific  bacterium  which  he  termed 
Streptohacillus  pellagrce,  which  he  isolated  from  spoiled  corn 
and  from  the  blood,  spinal  fluid,  and  tissues  of  pellagrins. 

This  organism  usually  appears  as  a  short  bacillus,  grows  both 
in  short  and  long  chains,  stains  readily  with  the  ordinary 
aniline  dyes  and  often  shows  polar  staining.  It  is  non-spore 
forming,  and  obtains  its  optimum  growth  on  human  or  rabbit 
blood  agar  at  37°C. 

The  main  arguments  advanced  by  the  zeists  for  their  beliefs 
as  to  the  etiology  of  pellagra  are  based  upon  the  following 
assumptions : 

1.  Pellagra  first  developed  in  Europe  almost  immediately 
subsequent  to  the  introduction  of  Indian  corn  from  America. 

2.  Pellagra  appeared  everywhere  that  corn  was  cultivated, 
and  the  number  of  cases  increased  as  the  new  grain  became 
more  popular  as  an  article  of  diet. 

3.  Pellagra  is  found  only  in  localities  where  corn  is  cultivated 
or  imported  and  only  in  individuals  who  consume  it  as  food. 

4.  And  finally,  since  the  institution  of  the  prophylactic 
measures  of  the  Italian  government  which  have  reduced  the 
consumption  of  spoiled  corn,  the  number  of  cases  of  pellagra 
has  diminished. 

The  anti-zeists  offer  the  following  arguments  against  the 
maize  theory: 


PELLAGRA  299 

1.  That  pellagra  first  appeared  in  Europe  soon  after  the 
introduction  of  corn  from  America  is  without  foundation  in 
fact. 

2.  That  many  districts  exist,  where  corn  has  been  cultivated 
and  used  as  an  article  of  diet  for  generations,  in  which  pellagra 
is  unknown. 

3.  That  pellagra  is  often  found  in  individuals  who  have 
seldom  or  never  partaken  of  corn  as  food. 

4.  That  the  peculiar  topographic  distribution  of  pellagra 
even  in  the  worst  endemic  centers  is  untenable  with  the  corn 
theory. 

5.  That  the  erythema  and  other  characteristics  of  the  disease 
may  recur  each  spring  for  several  years  in  patients  removed 
from  the  endemic  centers  and  who  have  been  on  a  corn-free 
diet. 

6.  That  all  prophylactic  measures  based  on  the  corn  theory 
have  failed  to  prevent  the  disease. 

Other  dietetic  factors  than  corn  have  from  time  to  time  been 
proposed  as  the  cause  of  pellagra.  Thus  Strombio,  as  far  back 
as  1784,  considered  bad  food  as  an  important  cause.  Others 
thought  the  lack  of  salts  in  the  diet  was  responsible,  while  by 
some  the  abstinence  from  wine  by  those  who  were  used  to  it 
was  considered  the  cause  of  the  disease. 

In  191 1  Mizell"*  proposed  the  theory  that  pellagra  was 
due  to  the  use  of  cotton-seed  oil;  this  theory  is  untenable  be- 
cause of  the  fact  that  cotton-seed  oil  is  not  used  as  an  article 
of  diet  by  the  vast  majority  of  European  pellagrins,  if  at  all, 
and  that  it  is  used  very  extensively  in  this  country  in  locaKties 
where  pellagra  is  unknown.  We  are  very  much  in  accord  with 
Lavinder,"''  who  states  that  the  publication  of  such  speculations 
founded  upon  personal  opinion,  especially  when  they  add  to 
the  fears  of  the  laity,  are  strongly  to  be  deprecated. 

Goldberger^"  in  1914  asserted  that  pellagra  is  a  disease 
essentially  of  dietary  origin  and  that  it  is  caused  in  some  way 
by  the  absence  from  the  diet  of  essential  vitomines  or  perhaps, 
as  is  suggested  by  the  work  of  Meyer  and  Voegtlin,  by  the 
presence  in  the  vegetable  food  of  such  poison  as  soluble 
aluminum  salts  in  excessive  amounts. 


300  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Goldberger  cites  as  evidence  of  the  correctness  of  his  theory 
the  fact  that  of  996  patients  admitted  to  the  Georgia  State 
Sanatorium  during  the  year  1910,  excluding  those  who  died, 
were  discharged  or  had  pellagra  upon  admission,  there  were 
remaining  in  the  institution  after  one  year  418  patients  and  of 
this  number  32  or  7.65  per  cent,  developed  the  disease.  He 
continues  that  none  of  the  293  employees  of  the  Sanatorium  who 
came  into  contact  with  the  pellagrins  developed  pellagra,  while 
if  the  disease  had  developed  in  the  employees  at  the  same  rate 
as  in  the  patients  22  of  them  should  have  been  afflicted. 

Further  studies  at  the  Jackson  orphanage  showed  that  68  or 
32  per  cent,  of  the  211  inmates  had  pellagra.  To  Goldberger 
the  remarkable  fact  to  be  observed  is  that  practically  all  of  the 
cases  developed  in  children  between  the  ages  of  6  and  1 2  years, 
that  only  2  cases  developed  in  the  group  of  25  children  under 
6  years  of  age  and  only  i  case  in  the  group  of  66  children 
over  12  years  of  age. 

Goldberger  found  that  in  both  the  institutions  cited  the 
groups  which  were  exempt  from  pellagra  subsisted  on  a  better 
diet  than  those  who  developed  the  disease,  that  the  diet  of  the 
pellagrin  was  noticeable  for  the  marked  lack  of  meat  or  other 
animal  protein  and  that  of  the  vegetable  food,  such  as  corn  and 
sirup,  were  in  excess  and  legumes  relatively  inconspicuous.  He 
therefore  concluded  that  this  one-sided  diet  is  the  cause  of 
pellagra. 

That  the  disease  develops  in  certain  groups  of  individuals 
outside  of  institutions  is  due  mainly  to  economic  conditions 
such  that  the  more  expensive  foods,  meat,  milk,  eggs,  legumes, 
etc.,  are  not  procurable  among  the  poorer  classes. 

That  it  develops  in  certain  well-to-do  individuals  is  accounted 
for  by  Goldberger  by  more  or  less  well-recognizable  eccentri- 
cities of  taste,  which  causes  them  to  partake  of  a  one-sided 
diet. 

He  further  states  that  such  eccentricities  of  taste  are  found 
in  the  insane,  some  of  whom  will  not  eat  at  all.  This,  Gold- 
berger thinks,  accounts  for  the  development  of  pellagra  among 
residents  of  insane  asylums  where  the  diet  is  otherwise 
satisfactory. 


PELLAGEA  3OI 

Goldberger  (547)  has  recently  conducted  a  feeding  experiment 
upon  eleven  convicts  on  the  Mississippi  State  Penitentiary  farm. 
These  men  were  fed  a  proteid-free  diet  from  April  19,  191 5  to 
October  31,  1915.  Of  the  eleven  subjects  not  less  than  six  are 
claimed  to  have  developed  symptoms,  including  a  typical 
dermatitis,  justifying  a  diagnosis  of  pellagra.  The  nervous 
and  gastro-intestinal  symptoms  are  said  to  have  been  mild  but 
distinct.  The  skin  lesions  were  first  recognized  on  the  scrotum. 
Later  there  appeared  lesions  on  the  backs  of  the  hands  in  two 
cases  and  on  the  back  of  the  neck  in  one  case. 

This  experiment  while  suggestive  would  have  proved  more 
convincing  had  it  been  conducted  in  a  pellagra-free  territory. 

The  theory  that  water  may  be  responsible  for  pellagra  is  an 
old  one,  and  many  attempts  have  been  made  to  connect  the 
etiology  of  pellagra  with  the  source  of  the  water  supply  of  the 
individual.  Numerous  investigators  have  collected  statistics 
of  this  nature,  and  many  theories  as  to  the  manner  in  which 
water  could  cause  the  disease  have  been  advanced. 

Quite  novel  among  these  theories,  however,  is  the  contention 
that  pellagra  is  due  to  the  presence  of  certain  chemical  sub- 
stances in  drinking  water. 

Alessandrini  and  Scala^^^  propounded  the  idea  that  the  etio- 
logical factor  of  pellagra  is  to  be  found  in  the  silica  in  the 
colloidal  state  contained  in  certain  potable  waters.  In  support 
of  their  view  they  cite  a  large  amount  of  experimental  data, 
the  work  being  conducted  on  guinea-pigs,  dogs,  rabbits  and 
monkeys.  They  injected  the  animals  with  and  caused  them 
to  drink  artificial  colloidal  solutions  and  gelatinous  suspensions 
of  silica  and  natural  potable  waters  of  various  pellagrous  dis- 
tricts. From  the  results  of  their  experiinents  they  conclude 
that  they  hav£  produced  in  animals  a  chronic  intoxication 
which  very  closely  simulates,  even  in  the  details,  pellagra  as 
seen  in  human  beings.  They  claim  to  have  produced  typical 
clinical  symptoms  as  well  as  typical  pathologic  findings. 

Infectivity. — The  second  great  etiologic  theory  of  pellagra, 
that  it  is  an  infectious  disease,  has,  especially  of  recent  years, 
received  the  enthusiastic  support  of  many  investigators.  There 
are    four  well-known    theories   concerning   the  infectivity  of 


302  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

pellagra:  first,  that  it  is  a  bacterial  disease;  second,  that  it 
is  a  parasitic  disease  transmitted  by  a  blood-sucking  insect; 
third,  that  it  is  a  form  of  amebiasis;  fourth,  that  it  is  a  parasitic 
disease  due  to  a  water-borne  nematode  worm. 

Contagion. — One  of  the  first  questions  asked  when  the  in- 
fectious theory  is  considered  is  concerning  the  contagiousness 
of  pellagra.  Can  non-pellagrins  associate  with  pellagrins 
without  fear  of  contracting  the  disease?  This  is  one  of  the 
most  important  questions  which  confronts  us  and  one  which 
cannot  be  answered  with  certainty.  Most  of  the  early  observers 
considered  pellagra  as  non-contagious,  although  by  some  it 
was  considered  to  be  spread  by  direct  contact. 

Marie,^"^  who  holds  so  rehgiously  to  the  corn  theory,  natu- 
rally does  not  believe  in  its  infectivity. 

Sambon^^*  says  pellagra  is  not  contagious  and  tells  of  having 
an  Italian  pellagra  girl  as  nurse  for  his  children,  and  this  inti- 
mate contact  failed  to  convey  the  disease  from  one  person  to 
another. 

Other  facts,  which  seem  to  refute  the  idea  of  contagion  are: 
first,  pellagra  is  usually  confined  within  certain  narrow  centers 
while  there  is  free  intercourse  between  the  inhabitants  of  these 
centers  and  those  of  neighboring  communities;  second,  pellagra 
is  very  rarely,  if  ever,  found  in  physicians,  nurses  or  attendants 
who  come  into  almost  daily  contact  with  pellagrins;  third, 
pellagra  is  never  transmitted  from  a  pellagrous  wet  nurse  to  a 
child,  or  from  a  pellagrous  child  to  a  healthy  mother. 

Krauss'^^  mentions  two  cases  which  bear  out  the  latter  con- 
tention :  one,  a  pellagrous  infant  of  twelve  months  of  age  which 
had  contracted  the  disease  at  the  age  of  six  months  and  had 
had  no  nourishment  except  the  milk  of  a  healthy  mother;  the 
other,  a  mother  with  a  virulent  pellagra,  had  nursed  an  infant 
for  four  weeks,  the  child  remaining  in  perfect  health. 

The  case  mentioned  above  under  other  predisposing  causes 
which  followed  pregnancy  and  puerperal  convulsions  is  of 
interest  also  in  this  connection.  Five  months  after  conception 
the  mother  who  has  active  symptoms  of  pellagra  is  nursing  the 
child  which  is  perfectly  normal. 

Family  Tendency. — The  opinion  of  most  observers  has  been 


PELLAGRA  3O3 

that  family  tendency  is  of  little  or  no  consequence  in  the  etiology 
of  pellagra,  and  that  by  far  the  vast  majority  of  pellagrins  are 
members  of  families  of  which  they  are  the  only  member  af- 
fected. Thus,  according  to  Roberts,^""  Alessandri  found  only 
five  families  with  more  than  one  pellagrin.  Lavinder^'^  found 
in  nearly  16,000  cases  more  than  one  case  to  the  family  933  times 
and  more  than  two  cases  235  times.  Grimm^^^  gives  the  follow- 
ing table  covering  this  point : 

(a)  Families  having  one  case  264 

(b)  Families  having  two  cases  23 

(c)  Families  having  three  cases  6 

(d)  Families  having  four  cases  i 

The  findings  of  the  Thompson-McFadden  Pellagra  Com- 
mission,^'* however,  are  sHghtly  at  variance  with  those  quoted 
above.  Of  316  cases  of  pellagra  they  found  160  or  50.6  per 
cent,  occurred  only  one  case  in  a  family,  84  or  26.6  per  cent, 
two  cases  in  a  family,  42  or  13.3  per  cent,  three  cases  in  a  family, 
20  or  6  per  cent,  four  cases  in  a  family,  and  10  or  3.2  per  cent, 
five  cases  in  a  family. 

One  case  which  we  have  seen  was  the  only  surviving  member 
of  a  family  of  four,  the  father,  mother  and  sister  having  died 
from  three  months  to  seven  years  previously  of  pellagra. 

Immunity. — When  the  various  facts  concerning  the  contagion 
and  family  incidence  of  pellagra  are  considered,  the  question 
of  immunity  naturally  arises. 

Sambon-'^  is  inclined  to  the  opinion  that  a  certain  kind  of 
immunity  is  acquired  by  residents  of  pellagrous  districts. 
This  he  thinks  is  especially  apparent  in  children,  as  pellagra  is 
more  prevalent  in  very  young  children  than  in  older  ones. 

Roberts'""  contends  that  there  is  probably  no  immunity 
either  natural  or  acquired  to  pellagra,  but  that  there  is  a 
variation  in  susceptibility. 

Bacterial  Disease. — The  theory  that  pellagra  is  a  disease 
caused  by  bacteria  other  than  those  of  corn  has  had  many 
enthusiastic  supporters,  and  many  attempts  to  isolate  the  in- 
fecting organism  both  microscopically  and  culturally  have  been 
made. 

Bravetta^"  after  exhaustive  cultural  studies  with  the  blood 


304  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

and  spinal  fluids  of  pellagrins  reached  the  conclusion  that  these 
are  sterile. 

MacNeal  and  Hamilton-^'  isolated  approximately  100  strains 
of  bacteria  from  the  intestines  of  pellagrins  and  subjected 
them  to  agglutination  tests  with  the  blood  serum  of  pellagrins. 
All  but  two  of  these  strains  reacted  negatively.  These 
two  strains,  however,  showed  a  very  definite  agglutination 
with  the  sera  of  pellagrins  in  the  acute  state  and  less  agglu- 
tination with  the  sera  of  pellagrins  taken  during  the  interval 
between  attacks.  The  possible  significance  of  these  facts  was 
much  lessened,  according  to  the  authors,  by  the  fact  that 
agglutination  occurred,  sometimes  as  definite  as  ^vith  pellagrins, 
with  the  sera  of  insane  non-pellagrous  patients  and  normal 
individuals. 

Early  in  191 5  Page^-°  announced  the  isolation  of  a  bacillus 
from  the  feces  of  pellagrins  which  he  insists  "must  be  the  cause 
of  the  disease."  According  to  this  author  the  organism  is 
from  4  to  10  microns  long  with  the  ends  more  sharpened  than 
those  of  the  colon  group.  It  is  a  spore  bearer  and  is  found  in 
many  forms.  Just  before  the  formation  of  a  spore  an  area  of 
cloudiness  or  bright  refraction  appears  and  the  bacillus  gener- 
ally elongates.  The  spore  grown,  the  membrane  of  the  bac- 
terium bursts  and  the  young  organism  emerges  through  the 
opening.  At  first  the  young  bacillus  is  very  active  and  as- 
sumes a  spiral  or  cork-screw  shape.  It  gradually  grows  in 
length  and  the  motility  decreases.  The  organism  is  aerobic 
and  Gram  negative.  Sterile  feces,  according  to  Page,  is  the 
best  culture  medium,  and  the  bacilli  grow  well  at  a  temperature 
of  80°  to  90°. 

Page  states  that  a  cat  fed  on  food  inoculated  with  pure 
cultures  developed  mild  diarrhea  and  nervousness,  and  that 
a  man  accidentally  infected  with  the  organism  developed 
pellagra. 

Page  says  that  he  has  found  the  organism  many  times  in 
sixty-four  cases  of  pellagra  and  that  he  has  been  unable  to  find 
it  in  normal  individuals  and  in  those  suffering  from  other 
diseases. 

Sanders'"  describes  a  similar  organism  which  he  isolated 


PELLAGRA  305 

from  the  spleen  of  a  pellagrin  at  necropsy  and  grew  on  a  special 
culture  media  containing  corn  meal.  He  considers  it  the  same 
organism  as  that  described  by  Page. 

Intermediate  Host. — The  theory  that  pellagra  is  an  insect- 
borne  disease  had  its  origin  with  Sambon,^^^  who  in  1905  stated 
before  the  British  Medical  Association  that  such  was  his  belief. 
He  later  incriminated  the  Simulium  reptans  as  the  offending 
insect  and  backed  his  theory  by  extensive  epidemiologic 
studies. 

Sambon  gives  as  his  reason  for  this  belief  the  following: 

1.  Pellagra  is  a  parasitic  disease  because: 

(a)  The  characteristic  eruption  and  other  symptoms  of  the 
disease  may  recur  each  spring  for  a  number  of  years,  notwith- 
standing the  removal  of  the  patient  from  the  endemic  districts 
and  the  strict  eHmination  of  maize  from  his  diet.  This  peculiar 
periodicity  of  symptoms  can  be  explained  only  by  the  agency 
of  a  parasitic  organism  presenting  definite  alternating  periods 
of  latency  and  activity.  Analogous  periodicities  are  met 
with  in  other  parasitic  diseases — as,  for  example,  in  tertian 
fever,  in  which  the  periods  of  activity  of  the  parasite 
{Plasmodium  vivax)  recur  each  summer  in  correlation  with  the 
activity  period  of  its  anophelic  definitive  host.  No  toxic 
substance  could  account  for  it. 

{b)  It  presents  the  peculiarities  of  distribution  and  seasonal 
incidence  found  in  all  parasitic  diseases. 

(c)  Its  symptoms,  course,  duration,  and  morbid  lesio-ns  are 
analogous  to  those  of  other  parasitic  diseases. 

2.  It  is  an  insect-borne  disease  because: 
(a)  It  is  not  directly  contagious. 

(6)  Neither  food  nor  drinking  water  accounts  for  its  pecuhar 
epidemiology. 

(c)  It  is  hmited  to  certain  rural  districts  only,  towns  and 
villages  almost  invariably  escaping. 

(d)  It  presents  a  definite  and  peculiar  seasonal  incidence — 
viz.,  spring  and  autumn. 

(e)  It  is  practically  restricted  to  only  one  class  of  people — 
viz.,  the  field  laborer,  owing  to  greater  exposure  to  infection. 

3.  It  is  conveyed  by  a  Simulium,  because: 


3o6  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

(a)  Simulium,  so  far  as  we  know,  appears  to  effect  the  same 
topographic  conditions  as  pellagra. 

(b)  In  its  imago  stage  it  seems  to  present  the  same  seasonal 
incidence. 

(c)  It  is  found  in  rural  districts  and,  as  a  rule,  does  not 
enter  towns,  villages,  or  houses. 

(d)  It  explains  most  admirably  the  peculiar  limitation  of  the 
disease  to  agricultural  laborers,  a  limitation  which  nothing  else 
can  explain  in  a  satisfactory  manner. 

(e)  It  has  a  wide  geographic  distribution  which  seems  to 
cover  that  of  pellagra,  although  certainly  exceeding  it,  in  the 
same  way  that  the  distribution  area  of  the  Anopheline  ex- 
ceeds that  of  malaria,  and  the  range  of  Stegomyia  calopus  that 
of  yellow  fever. 

(y)  It  is  known  to  cause  severe  epizootics  in  Europe  and 
America. 

{g)  Other  similarly  minute  blood-sucking  diptera,  such  as 
Phlebotomns  papatassi  and  Dilophus  feverilis,  are  strongly 
suspected  of  being  propagators  of  human  diseases. 

While  Sambon  does  not  state  definitely  the  nature  of  the 
hypothetical  infecting  organism  transmitted  by  the  sand-fly, 
he  is  inclined  to  regard  it  protozoal  in  nature. 

Since  the  formulation  of  Sambon's  theory  many  investigators 
have  written  pro  and  con  concerning  it  and  much  valuable 
information  has  been  obtained. 

Babes, -^^  who  holds  to  the  corn  theory,  considers  that  the  fact 
of  being  unable  to  find  any  relation  between  the  Simulium  and 
corn  is  sufficient  reason  for  discarding  Sambon's  theory. 

Roberts'"  discards  the  theory  of  Sambon,  that  the  etiologic 
factor  of  pellagra  is  borne  by  the  sand-fly,  and  incriminates  the 
mosquito.  He  bases  his  opinion  on  alleged  analogies  of  pellagra 
and  the  mosquito.  He  does  not  accuse  any  one  species  of  this 
insect,  but  states  that  it  will  probably  prove  to  be  a  rural- 
breeding,  house-living,  day-biting  mosquito.  Jennings  and 
King^'°  after  a  most  exhaustive  study  of  the  insects  of  Spartan- 
burg, S.  C,  including  ticks,  lice,  bedbugs,  cockroaches,  horse- 
flies, fleas,  mosquitoes,  buffalo  gnats  (Simulium),  house-flies, 
and  stable  flies  (Stomoxys),  reach  the   following   conclusion: 


PELLAGRA  307 

Horseflies  have  nothing  and  cockroaches  little  to  support  them 
as  the  intermediate  host. 

On  account  of  their  scarcity  and  the  nature  of  their  biting 
habits  ticks  and  fleas  may  be  excluded.  It  is  even  doubtful 
if  the  existence  of  an  animal  reservoir  of  infection  would  cause 
these  insects  to  become  prominent. 

The  sex  and  age  incidence  and  the  rural  nature  of  the  disease 
cannot  be  accounted  for  by  lice  and  bedbugs.  Further,  lice  are 
rather  scarce.  Mosquitoes  are  eliminated  on  account  of  their 
comparative  rarity,  the  night-biting  habit  of  the  local  species, 
which  would  not  account  for  the  sex  incidence,  and  the  lack 
of  coincidence  between  their  distribution  and  that  of  pellagra. 

House-flies  {Miisca  domestica)  are  considered  from  the 
point  of  view  that  pellagra  may  be  an  intestinal  infection,  the 
organisms  being  passed  with  the  feces  and  infecting  others 
through  contaminated  food. 

Buffalo  gnat  {Simidium)  could  hardly  have  been  considered 
had  it  not  been  for  Sambon's  theory.  In  Spartanburg  County 
they  seldom  attack  man,  and  when  they  do  it  is  only  locally  and 
their  attacks  are  largely  confined  to  field  workers.  Further, 
they  are  present  in  this  locality  only  in  comparatively  moderate 
abundance. 

In  the  stable  fly  (Stomoxys  calcitrans)  is  found  certain  promi- 
nent peculiarities  which,  according  to  Jennings  and  King, 
lead  them  to  consider  it  a  possible  intermediate  host  of  pellagra. 

The  range  of  the  stable  fly  covers  and  exceeds  that  of  pellagra. 
While  the  season  of  the  greatest  numbers  of  the  stable  fly  is 
somewhat  later  than  the  season  of  greatest  prevalence  of  pel- 
lagra, it  however  appears  earher  in  the  spring  than  do  most 
recurrences  and  new  cases  of  the  disease,  and  when  these  do 
occur  the  stable  fly  is  found  in  great  numbers.  This  insect  is 
exceedingly  plentiful  and  is  found  most  in  rural  districts,  thus 
corresponding  to  the  rural  distribution  of  pellagra. 

On  account  of  the  great  number  of  stable  flies  it  seems  an 
efficient  transmitter  of  disease. 

The  stable  fly  is  intimately  associated  with  man  whom  it 
bites  often  and  persistently.  It  is  a  day-biting  insect,  which 
explains  the  sex  and  age  incidence.     The  life  of  the  stable  fly 


'308  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

seems  long  enough  for  the  development  of  a  possible  infecting 
organism. 

This  insect  is  easily  and  often  transported  over  long  distances, 
which  may  account  for  the  development  of  sporadic  cases  of 
pellagra. 

Amebiasis. — In  1909  Siler  and  Nichols-^^  called  attention  to 
the  large  number  of  pellagrins  in  whom  amebse  were  found. 

Jelks'-^  reported  having  found  amceba  histolytica  in  the 
mucopurulent  material  taken  from  the  rectum  of  a  pellagrin. 

Long^-^  proposed  the  hypothesis  that  pellagra  is  a  disease  due 
to  the  injury  of  the  intestinal  mucosa  caused  by  amebas,  and 
in  support  of  this  theory  reported  finding  the  ameba  in  the 
stools  of  fifty  out  of  fifty- two  pellagrins,  and  that  the  ulceration 
and  damage  to  the  intestine  was  shown  by  the  presence  of 
blood,  mucus  and  pus  in  the  feces. 

Nematode  Worm. — To  Alessandrini^-^  is  due  the  theory  that 
pellagra  is  due  to  a  water-borne  nematode  worm  which  he  found 
constantly  in  shallow  wells  and  slowly  flowing  streams  of  pel- 
lagrous regions.  These  were  found  only  rarely  or  were  entirely 
absent  from  the  potable  waters  of  non-pellagrous  districts. 
Later  Alessandrini  was  forced  to  abandon  this  theory  and  while 
he  continued  to  incriminate  potable  waters,  he  adopted  the 
colloidal  silica  theory  mentioned  above. 

Inoculation  Experiments. — As  far  back  as  1780  Gherardini 
attempted  the  inoculation  of  healthy  individuals  with  pellagrous 
material,  such  as  ichorous  matter  from  the  skin  lesions,  the  blood 
and  saliva,  but  with  negative  results. 

Since  that  time  numerous  attempts  have  been  made  to 
reproduce  pellagra  in  the  lower  animals. 

In  1910  Anderson  and  Goldberger^-^  attempted  to  infect  the 
Rhesus  monkey  with  the  blood  and  spinal  fluid  of  pellagrins. 
Similar  experiments  were  conducted  by  Lavinder^^'  and  by 
Singer,  MacNeal  and  Rooks,^^*  all  with  negative  results. 

In  the  summer  of  1913,  however,  came  the  announcement  of 
Harris^-^  of  New  Orleans  that  the  experimental  production  of 
pellagra  in  the  monkey  had  been  accomplished.  The  tissues 
from  different  parts  of  the  body,  central  nervous  system, 
portions  of  skin  lesions  and  alimentary  tract,  were  removed  at 


PELLAGRA  309 

necropsy  soon  after  death  from  a  typical  case  of  pellagra. 
After  mixing  with  an  equal  amount  of  normal  saline  solution 
and  ground  in  a  mortar  they  were  allowed  to  stand  in  the  ice 
chest  over  night.  They  were  then  coarse  filtered  and  the  juice 
passed  through  a  Berkefeld  filter,  Letter  N.  The  filtrate  was 
injected  subcutaneously,  intravenously  and  intracranially  in 


Fig.   68. — Monkey  2,  shomng  lesions  of  face.      (Courtesy  of  Dr.  W.  H.  Harris.) 

large  quantities  into  monkeys  (Macacus  rhesus).  The  first 
of  these  animals  remained  apparently  normal  for  many  months 
when  he  developed  irregular  dark  patches  on  the  hands,  fore- 
arms, face,  back  and  sides  of  the  body.  He  gradually  became 
emaciated  and  weak  and  finally  died  "with  all  the  signs  of 
pellagra." 

The  second  monkey  after  a  period  of  about  three  months 
developed  similar  lesions  to  monkey  i,  and  at  the  time  of  pub- 
lication was  still  living,  though  growing  progressively  weaker 
and  thinner. 

Stimulated  by  this  work  of  Harris,  Lavinder,  Francis,  Grimm 
and  Lorenz^^^  attacked  the  problem  anew  and  by  103  experi- 
ments with  77  rhesus  monkeys,  2  Java  monkeys  and  3  female 
baboons  administered  pellagrous  material  from  every  conceiv- 


3IO 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


able  source  and  in  every  conceivable  manner.  The  pellagrous 
material  consisted  of  tissue  extracts,  pericardial  and  spinal 
fluids  from  necropsies,  and  blood,  urine,  feces  and  spinal 
fluid  collected  during  life. 

f 


Fig.  6g. — Monke>' 


sho\Mn_;  liMon,  o(  hands  and  face. 
Dr   W  .  H    Harris.) 


(Courtesy  of 


The  inoculations  were  made  intravenously,  intraperitoneally, 
intraspinally  and  material  was  fed  by  stomach  tube. 

Eight  of  the  animals  died  after  varying  periods  following 
inoculation.  Four  of  them  showed  plainly  death  was  not  due 
to  pellagra.  The  cause  of  death  was  not  determined  in  the 
other  four. 

The  remaining  monkeys  with  one  exception  had  up  to  the  time 


PELLAGRA  3II 

of  the  publication  of  the  report  shown  no  indications  suggesting 
pellagra. 

The  following  is  the  history  of  the  exception: 

M.  Rhesus,  98,  was  injected  intraspinally  with  6  c.c.  of  spinal 
fluid,  April  14,  1914,  and  again  inoculated,  May  2,  intraspinally 
with  4  c.c.  of  spinal  fluid  drawn  from  another  pellagrin.  The 
first  change  in  this  monkey  was  noted  May  4,  1914,  at  which 
time  the  right  forearm  appeared  slightly  swollen  and  looked 
as  though  some  of  the  hair  was  falling  out.  The  following 
day  the  left  forearm  showed  a  similar  condition.  Later  both 
forearms  became  entirely  denuded  of  hair,  the  skin  became 
roughened  and  scaly  with  red  cracks  in  which  appeared  a 
slight  serous  exudate.  Over  both  wrists  the  superficial  skin 
seemed  to  be  denuded  and  the  condition  gave  the  appearance 
of  superficial  ulceration.  On  the  posterior  surface  of  each  hand 
a  similar  condition  was  noticed;  the  knuckles  of  the  fingers  were 
swollen  and  reddish  and  presented  cracks  and  broken  skin. 
May  9  the  skin  was  dry  and  more  scaly.  The  bowel  movements 
were  occasionally  loose.  Later  thick  crusts  on  the  skin  came 
away,  leaving  a  pale  and  slightly  scaly  surface.  The  monkey 
is  now  again  in  his  usual  condition. 

These  investigators  admit  that  the  interpretation  of  the 
above  manifestations  is  not  clear  and  state  that  they  may  be 
accidental  or  that  they  may  indicate  pellagra.  If  they  do 
indicate  pellagra  they  were  brought  about  either  by  a  living 
organism  or  by  an  unorganized  toxic  element. 

Pathogenesis. — The  subject  of  the  pathogenesis  of  pellagra 
as  with  every  other  disease  is,  of  course,  intimately  associated 
with  the  etiologic  factor,  and  until  this  is  determined  any 
statements  concerning  this  feature  of  the  disease  must  perforce 
be  little  more  than  conjectures. 

The  sun  has  long  been  accused  of  exerting  some  influence 
over  pellagra  and  has  even  been  considered  the  sole  etiological 
factor.  Sandwith^^^  says  the  sun  is  certainly  responsible  for 
some  of  the  skin  eruption. 

As  stated  above  those  who  hold  to  the  photodynamic  theory 
consider  that  the  sun's  rays  acting  on  the  exposed  surfaces  of 
the  body  sensitize  a  hypothetical  toxin  of  ingested  corn. 


312  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

It  has  been  suggested  that  the  actinic  rays  of  the  sun  are 
responsible  for  the  erythema  and  others  consider  the  direct 
heat  of  the  sun  the  cause.  It  is  a  fact  that  those  pellagrins 
who  are  more  exposed  to  the  sun's  rays  usually  develop  the 
skin  eruption  before  the  onset  of  the  other  manifestations  and 
those  who  are  well  protected  from  the  sun  usually  develop  the 
gastro-intestinal  and  other  symptoms  before  the  erythema. 
Nevertheless  it  is  not  the  sun  which  causes  the  erythema  but  the 
pellagra.  Allessandrini  and  Scala'^'  who  proposed  the  theory  of 
silica  in  drinking  water  contend  that  there  is  more  or  less  afhnity 
for  mineral  salts  exhibited  by  colloidal  silica  and  they  conclude 
from  their  experiments  on  dogs  that  "without  doubt  silica 
in  the  animal  organism  acts  by  accumulating  mineral  substances 
and  produces  in  consequence  a  destruction  of  tissues."  They 
trace  the  chemical  changes  and  relations  which  the  silica  under- 
goes and  further  conclude.  "Therefore  it  seems  to  us  without 
doubt  that  the  silica  fixes  the  mineral  salts  on  the  proteins  of 
the  tissues  with  a  continuous  incessant  action  quite  similar 
to  the  action  of  an  enzyme  or  diastase." 

They  finally  arrive  at  the  following  conclusion,  that ' '  pellagra  is 
a  malady  caused  by  the  forced  retention  of  mineral  salts  which 
in  turn  produces  a  liberation  of  acids  in  excess  of  the  needs  of 
the  particular  organism ;  or  in  other  words,  pellagra  is  nothing 
more  than  a  mineral  acidosis  with  all  of  its  consequences." 

Gosio  and  Anatonini-^^  contend  that  pellagra  is  a  form  of 
anaphylaxis,  that  the  organism  becomes  sensitized  by  the 
toxins  produced  by  the  parasitic  moulds  of  Indian  corn,  and 
that  repeated  ingestion  of  these  toxins  brings  on  the  phenomena. 

Long^-*  who  proposed  the  ameba-intoxication  theory  of 
the  disease  assumed  that  the  skin  lesions  are  caused  by  pressure 
on  the  nerves  at  their  exit  from  the  spinal  canal  due  to  a  deposit 
in  the  foramina,  and  to  degeneration  of  the  nerves  themselves 
as  a  result  of  toxemia. 

Jelks'^"  thinks  that  pellagra  is  not  a  morbid  entity  but  a 
series  of  symptoms-complex,  due  to  the  absorption  of  certain 
toxins  or  toxin-developing  bacteria  carried  into  the  blood 
stream  or  to  the  central  nervous  system  by  ameba  which  he 
claims  are  almost  constantly  found  in  these  cases. 


CHAPTER  XIX 
PATHOLOGY  OF  PELLAGRA 

The  pathology  of  pellagra  presents  no  characteristic  features 
which  are  absolutely  constant,  but  certain  morbid  changes 
usually  take  place  which  serve  as  distinguishing  factors. 
For  example,  there  is  usually  anemia  and  more  or  less  emacia- 
tion, but  we  have  seen  pellagra  in  well-nourished  individuals. 
Again  the  eruption  is  a  very  constant  manifestation  but 
"pellagra  sine  pellagra"  is  not  unknown. 

The  pathologic  findings  described  are  usually  those  of  the 
skin,  gastro-intestinal  tract  and  the  central  nervous  system, 
although  other  organs  and  tissues  are  frequently  involved. 

Skin. — The  skin  lesions  are  more  or  less  characteristic. 
Among  foreign  writers,  and  to  some  extent  among  those  of 
America  also,  it  is  customary  to  divide  the  skin  manifestations 
into  three  stages,  viz. :  first,  the  stage  of  congestion  or  erythema; 
second,  the  stage  of  thickening,  pigmentation  and  added 
scaliness;  and  third,  the  stage  of  atrophy.  To  us  this  seems 
an  artificial  classification  and  that  the  skin  manifestations  of 
pellagra  do  not  present  stages,  so  much  as  degrees  of  the 
lesions. 

The  lesions  of  the  skin  in  pellagra  usually  start  as  mild  ery- 
thema scarcely  distinguishable  from  the  erythema  of  sunburn. 
They  may,  however,  as  Merk  has  shown,  start  as  discreet 
maculae  which  last  for  a  few  days  to  a  few  weeks.  The  pellagra 
erythema  is  of  a  vivid  red  color  and  perhaps  slightly  darker  in 
shade  than  erythema  of  sunburn.  After  a  variable  period  of 
time  a  hyperkeratosis  may  take  place  and  the  lesions  are  covered 
with  scales  and  shed-off  epithelium.  As  a  result  of  this  process 
the  tissues  are  swollen  due  to  the  increase  of  blood  and  serum 
to  the  derma,  causing  the  skin  to  have  a  wrinkled  appearance. 
In  some  instances  there  is  a  pigmentation  following  the  desqua- 
mation while  in  others  the  skin  is  of  lighter  hue  than  before. 
313 


314  ENDEMIC    DISEASES    OE    THE    SOUTHERN    STATES 

Frequently,  instead  of  a  hyperkeratosis,  there  may  be  super- 
imposed upon  the  erythema  vesicular  or  bullous  lesions.  These 
may  be  quite  large  in  size  and  are  always  monolocular.  In 
a  few  days  they  gradually  dry,  leaving  a  thickened  crusted 
condition  of  the  skin.  This  class  of  lesions  is  not  infrequently 
the  seat  of  secondary  pyogenic  infection.  Often  the  edema 
is  sufficient  to  produce  marked  fissures. 

It  not  infrequently  occurs  that  the  bulla  is  broken  by 
mechanical  action  and  the  surface  of  the  lesion  appears  raw 
and  bleeding.  After  this  class  of  lesion  has  cleared,  the  skin 
is  somewhat  thinner  than  formerly  and  there  is  no  pigmentation. 

The  microscopic  picture  of  the  skin  in  pellagra  is  one  very 
similar  to  erythema  multiforme.  It  is  evidently  due  to  dis- 
turbances of  the  nervous  system  and  the  peripheral  circulatory 
apparatus;  in  other  words,  it  is  an  angioneurosis. 

The  greatest  pathologic  change  is  seen  in  the  superficial  part 
of  the  corium,  the  most  marked  infiltration  being  found  in  the 
stratum  papillare. 

With  low  power  magnification  the  stratum  corneum  is  seen 
to  be  more  or  less  thickened  while  the  stratum  granulosum  and 
the  rete  Malpighii  are  usually  not  involved.  The  upper  portion 
of  the  corium  usually  shows  a  considerable  inflammatory  proc- 
ess while  the  subcutaneous  tissue  is  more  or  less  edematous. 
With  the  higher  magnifications  the  hypertrophy  of  the  corneum 
is  seen  to  be  quite  marked.  Usually  more  or  less  parakeratosis 
is  demonstrable  by  the  finding  of  nucleated  cells  in  the  upper 
layer  of  the  corneum,  and  pigment  granules  are  seen  scattered 
through  it.  The  only  pathologic  finding  in  the  rete  Malpighii 
is  a  shght  infiltration  of  cells.  The  most  marked  cellular  in- 
filtration is  seen  in  the  pars  papullaris,  especially  around  the 
blood-vessels.  Collagen,  showing  edematous  change  and  elastin 
are  seen.  The  other  layers  of  the  corium  show  little  or  no 
pathologic  change. 

Gastro-intestinal  Tract. — Here  again,  as  with  the  skin  lesions, 
the  pathologic  findings,  while  usually  quite  marked,  have  no 
absolutely  characteristic  features. 

The  tongue  is  usually  swollen  and  more  or  less  denuded  and 
nearly  always  presents  a  bright  red  appearance.     Along  the 


PELLAGRA  31S 

edges  and  on  the  undersurface  ulcerated  areas  may  be  seen 
and  sometimes  yellowish  sloughs  which  bleed  easily  are  found. 
The  lips  and  cheeks  also,  in  the  worst  cases  show  similar  ulcera- 
tion and  sloughing. 

The  stomach  often  shows  a  chronic  gastritis.  The  mucosa  is 
frequently  found  pale,  while  there  is  more  or  less  atrophy  of  the 
muscular  coat. 

The  intestines  usually  show  a  similar  condition.  There  may 
be  either  anemia  or  hyperemia.  Ulcers  may  be  found  along  the 
entire  tract  but  are  more  frequently  seen  in  the  ileum  and 
jejunum.  There  is  usually  a  thickening  of  Peyer's  patches  and 
the  mesenteric  lymph  glands  are  often  markedly  enlarged. 

The  histopathology  of  the  gastro-intestinal  tract  in  pellagra 
presents  nothing  absolutely  characteristic.  Sections  of  the 
tongue  show  a  similar  picture  to  sections  of  the  skin.  There  is 
a  desquamation  of  the  epithelium  and  some  infiltration  of  the 
tunica  propria. 

Sections  of  the  stomach  wall  show  more  or  less  superficial 
necrosis  with  destruction  and  exfoliation  of  the  glandular  epi- 
thelium. The  gland  tubules  may  show  cystic  dilatation  with 
infiltration  of  connective  tissue  between  them.  The  blood- 
vessels of  the  submucosa  are  usually  dilated,  while  the  muscular 
coats  are  more  or  less  atrophied.  As  a  rule  the  condition  is 
less  marked  in  the  cardiac  end  than  in  the  pyloric  end. 

The  microscopic  picture  of  the  intestines  shows  chronic  in- 
flammation with  atrophy  and  disappearance  of  some  of  the 
columnar  cells.  There  is  sometimes  entire  destruction  of  the 
epithehum,  only  a  narrow  line  of  necrotic  tissue  marking  its 
location. 

Central  Nervous  System. — The  most  exhaustive  study  of  the 
pathologic  anatomy  of  the  central  nervous  system  which  has 
been  made  in  this  country  is  that  of  Singer  and  Pollock.''^ 

These  investigators  found  that  the  dura  mater  is  usually 
thickened,  streaked  with  increased  formation  of  connective 
tissue  and  sometimes  adherent  to  the  pia  mater.  The  pia- 
arachnoid  is  found  to  be  cloudy,  opaque,  edematous  and. 
thickened.  This  is  most  marked  over  the  convexity  of  the 
brain,  and  at  times  the  membranes  are  separated  from  the 


3l6  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

brain  by  the  collection  of  fluid.  Occasionally  instead  of  being 
separated  from  the  brain  by  fluid  the  pia-arachnoid  is  adherent 
to  the  cortex.  In  the  meninges  of  the  spinal  cord  are  seen 
similar  pathologic  findings  to  those  found  in  the  cerebrum. 
Small  bony  plaques  are  sometimes  noted.  No  abnormalities 
are  found  in  the  basal  ganglia,  cerebellum,  pons  and  medulla 
as  a  rule. 

1.  Pia  Mater. — Microscopically  the  pia  always  shows  rather 
marked  change  consisting  of  a  thickening  of  the  connective 
tissue  with  a  proliferation  of  the  fibroblasts.  Occasionally 
the  gha  of  the  cortex  invades  the  pia,  especially  in  the  neigh- 
borhood of  the  sulci.  The  most  marked  changes  are  found  in 
the  blood-vessels.  An  exudate,  consisting  of  cells  which  are 
swollen  and  undergoing  fatty  degeneration,  and  fibrinoid  pig- 
ment granules  and  lymphocytes,  is  often  seen.  This  exudate  is 
scanty  compared  with  that  found  in  cerebral  syphilis,  paresis, 
etc.  These  changes  in  the  pia  are  most  pronounced  over  the 
convexity  of  the  brain  and  very  rarely  are  severe.  Similar 
findings  are  observed  in  the  pia  mater  of  the  spinal  cord. 

2.  Blood-vessels. — Singer  and  Pollock  describe  the  pathologic 
changes  which  are  found  in  the  blood-vessels  under  two  head- 
ings, acute  and  chronic,  and  state  that  the  former  may  be  re- 
lated to  pellagra,  while  the  latter  certainly  are  not. 

The  larger  arterioles  show  the  most  evidence  of  chronic 
change.  All  the  coats  of  the  vessel  are  thickened  while  there 
is  some  proliferation  of  the  cells,  which  are  swollen  and  fre- 
quently are  found  to  contain  pigment  granules.  Some  en- 
dothelial cells  of  the  intima  also  are  swollen  and  often  contain 
granules  due  to  degeneration.  The  vessels  are  usually  sur- 
rounded by  numerous  fatty  and  fibrinoid  granules,  and  some- 
times basophilic  granules  are  seen.  Granule  cells  {Ahraum- 
zellen)  containing  fatty  and  fibrinoid  material  are  very  often 
noted.  In  the  smallest  vessels  also  is  seen  to  some  extent 
the  chronic  thickening  and  occasionally  splitting  of  the  intima. 
Neither  hyaline  change  of  the  vessel  wall  nor  occlusion  of  the 
lumen  is  noted. 

The  smallest  vessels  present  the  more  acute  changes.  The 
intima  is  thickened  by  proliferation  of  the  endothelial  cells 


PELLAGRA  317 

which  are  found  either  swollen  or  shrunken.  Fatty  degenera- 
tion is  frequently  seen  and  often  the  intima  is  spht,  although 
few,  if  any,  cells  are  found  in  the  spaces  thus  formed.  Pro- 
liferation, with  swelling  and  distortion,  of  the  muscle  cells  is 
seen.  These  are  elongated,  poor  in  chromatin  and  contain 
pigment  of  various  kinds.  Thickening  of  the  adventitia  with 
proliferating  and  degenerating  cells  is  noted.  Singer  and 
Pollock  state  that  in  some  cases  these  changes  are  very  slight. 

These  authors  tell  of  a  whole  set  of  specimens  from  one  case 
in  which  were  found  in  the  adventitial  cells  a  number  of  meta- 
chromatic basophile  bodies  presenting  various  shapes;  "rosettes 
curved  and  elongated  masses  with  small  projecting  buds  or 
lobules,  etc."  They  further  state  that  these  bodies  resemble 
very  closely  the  bodies  described  by  Borrel  in  carcinoma,  and, 
slightly.  Councilman's  variola  bodies.  They  stained  a  purp- 
lish red  with  thionin,  similar  in  color  to  the  nucleus  of  the  speci- 
mens but  as  these  authors  were  unable  to  demonstrate  them 
again  with  an  apparently  identical  technic  they  conclude  that 
if  they  were  not  degenerative  products,  they  were  cell  nuclei. 

Singer  and  Pollock  state  that  in  all  cases  there  is  more  or  less 
perivascular  infiltration.  This  consists  of  vessel  cells,  pig- 
mented and  degenerating  lymphocytes,  fatty  and  fibrinoid 
pigment  granules,  glia  cells  and  granule  cells.  No  basophile 
cells  are  noted,  and  no  example  of  etat  crible  or  blood  cyst  was 
seen.  These  authors  state  that  there  is  nothing  in  the  picture 
to  indicate  a  local  invasion  of  the  nerve  tissue  with  micro- 
organisms. 

3.  Neuroglia. — (a)  Fibers.  Increase  of  the  glia  fibers  is 
noted  in  the  outermost  layer  of  the  cortex,  especially  prominent 
in  and  about  the  sulci  and  around  the  blood-vessels.  Numer- 
ous amyloid  bodies  are  observed  among  these  fibers.  The 
glia  fibers  sometimes  are  found  in  the  pia  mater  and  cause  it 
to  adhere  to  the  cortex.  This  proliferation  of  the  glia  fibers 
is  also  noted  in  the  spinal  cord,  especially  marked  around 
the  periphery  and  the  central  canal.  Singer  and  Pollock  state 
that  while  this  increase  of  the  glia  fibers  is  sometimes  quite  ex- 
tensive it  is  never  found  as  great  as  usually  found  in  senile 
dementia. 


3l8  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

{b)  Cells.  In  regard  to  the  cells  it  is  stated  that  while 
several  types  of  glia  nuclei  and  cell  bodies  with  thionin  staining 
are  found  no  definite  conclusions  can  be  drawn  from  them, 
since  the  normal  limits  of  these  cells  are  not  well  known.  A 
large  number  of  pyknotic  distorted  cells  with  long  fibers, 
"star-shaped  lanceolate,  biscuit-shaped,  and  semilunar"  nuclei 
are  seen  in  the  superficial  layers  of  the  cortex.  The  proto- 
plasm of  the  cells  takes  stains  poorly,  while  many  bluish-red 
or  pink-staining  granules  are  observed.  The  deeper  layers  of 
the  cortex  present  glia  cells  containing  a  small  dark  nucleus 
rich  in  chromatin,  and  a  small  amount  of  poorly  staining 
protoplasm.  Here  also  are  found  cells  with  a  pale  nucleus  often 
swollen  and  distorted  and  filling  almost  the  entire  cell,  con- 
taining a  few  fine  chromatin  granules  and  sometimes  one  or 
two  pink-staining  nucleolus-like  bodies.  Occasionally  a  cell 
with  a  similar  nucleus  but  with  deeply  staining  protoplasm  is 
seen.  Two  types  of  cells  are  seen  in  the  white  matter,  one  con- 
taining a  small  dark  nucleus,  while  the  other  contains  a  large 
pale  one.  In  the  bodies  of  the  glia  cells  of  the  cortex  is  noted 
marked  fatty  degeneration  and  pigment  material  staining  blue, 
green  and  reddish  with  thionin. 

SatelHtosis  is  said  by  Singer  and  Pollock  to  be  constantly 
present  in  a  varying  degree  depending  on  the  amount  of  chronic 
change  in  the  ganglion  cells.  The  satellites  are  sometimes 
found  directly  around  a  ganglion  cell,  even  forming  a  fence 
around  it  leaving  a  space  between  them  and  the  cell.  Satel- 
Htosis is  most  marked  about  the  cells  undergoing  degeneration 
and  also  the  shadow  cells.  It  is  not  present  about  the  cells 
showing  axonal  reaction. 

The  astrocytes  are  said  always  to  be  increased  in  number, 
but  especially  so  in  the  deeper  layers  of  the  cortex  and  the 
white  matter.  This  condition,  however,  is  not  so  marked  as 
in  paresis  or  senile  dementia. 

When  stained  by  Alzheimer's  Methods  IV  and  V  the  cell 
processes  are  usually  thickened  and  show  darkly  staining  streaks 
of  wavy  outHne,  although  they  may  be  small  and  thin  and  are 
frequently  broken.  The  cell  bodies  vary  in  size.  The  large 
ones  are  more  homogeneous.     The  protoplasm  often  contains 


PELLAGRA  319 

granules  corresponding  to  the  Alzheimer  methyl-blue  granules 
which  probably  is  a  degenerative  condition.  Variously  shaped 
nuclei  containing  granules  are  seen. 

Some  of  the  astrocytes  are  observed  near  but  parallel  to  the 
blood-vessels;  others  encircle  them,  but  seem  to  bear  no  relation 
to  them. 

In  some  cases  cystic  degeneration,  not  fatty,  is  seen.  The 
significance  of  this  condition  is  in  doubt,  but,  according  to 
Singer  and  Pollock,  it  suggests  a  degenerative  condition. 
Rarely  giant  astrocytes  are  found.  These  investigators  state 
that  while  the  increase  in  the  astrocytes  is  less  than  found  in 
senile  dementia  they  take  issue  with  Kozowski  in  his  assertion 
that  this  increase  is  the  exception  rather  than  the  rule.  They 
further  state  that  the  significance  of  the  increase  in  astro- 
cytes is  undetermined.  According  to  Alzheimer,  Wever  and 
Schroeder  it  would  seem  to  indicate  the  presence  of  an  active 
process,  while  Orlow  and  others  consider  them  more  numerous 
in  chronic  conditions. 

Alzheimer  considers  of  great  importance  the  finding  of  the 
ameboid  transformation  of  astrocytes  and  small  glia  cells, 
which  are  found  by  him  mainly  in  recent  and  active  diseases  of 
the  brain,  such  as  infection  deliria,  alcoholic  delirium,  dementia 
prsecox  in  the  acute  stages,  paresis,  cerebral  syphilis,  etc.,  and 
never  in  old  standing  softening,  old  hemorrhages,  old  dementia 
prascox,  etc. 

Singer  and  Pollock  state  that  these  ameboid  glia  cells  are 
found  in  pellagra,  often  clinging  to  a  vessel  by  means  of  the 
insertion  process,  but  they  draw  no  conclusions  from  such 
findings. 

4.  Nerve  Cells. — The  most  marked  changes  in  the  cells  of 
the  cortex  are  found  in  the  large  pyramidal  cells,  which  consist 
of  a  decrease  in  the  number  of  cells,  changes  in  their  relative 
positions,  and  an  increase  in  the  glia  elements. 

The  changes  in  the  ganglion  cells  are  most  marked  and  are 
considered  by  Singer  and  Pollock  of  great  importance.  These 
changes  they  divide  into  two  classes:  (i)  the  indirect  or  axonal 
types  of  reaction,  and  (2)  the  direct  types. 

I.  In  the  indirect  or  axonal  reactions  two  grades  of  intensity 


320  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

are  seen,  the  first  or  typical  reaction  in  which  the  cell  is  swollen 
and  rounded,  the  nucleus  displaced  to  the  periphery,  distorted, 
staining  more  or  less  uniformly  with  a  pale  color  and  containing 
a  well-preserved  nucleolus  rich  in  chromatin;  and  the  second 
or  central  chromatolysis,  in  which  the  cells  are  not  swollen, 
the  nucleus  is  well  reserved  with  a  darkly  staining  nucleolus, 
and  showing  a  marked  disappearance  of  the  Nissl  granules 
from  the  central  portion  of  the  cell. 

These  changes  are  most  marked  in  recent  cases,  that  is,  in 
those  dying  during  or  soon  after  an  acute  attack. 

Singer  and  Pollock  state  that  the  cells  showing  axonal  reac- 
tion are,  except  in  very  severe  degrees,  capable  of  recovery 
and  that  the  findings  are  probably  due  to  the  condition  which 
causes  the  acute  pellagrous  attack. 

The  widespread  axonal  chromatolysis  involving  especially 
the  Betz  cells  and  those  of  the  column  of  Clark  has  been  ob- 
served by  all  workers  in  pellagra  with  modern  methods  of 
staining.  Singer  and  Pollock  state,  however,  that  this  picture 
is  identical  to  the  one  described  by  Meyer  as  central  neuritis, 
and  to  one  seen  by  them  in  a  case  of  alcoholism  in  which  there 
was  nothing  to  suggest  a  history  of  pellagra.  They  therefore 
conclude  that  pellagra  is  not  recognizable  post-mortem,  except 
by  finding  typical  skin  lesions,  although  this  is  contrary  to  the 
opinion  of  Kozowski.  Singer  and  Pollock  further  state  that 
these  changes  can  be  interpreted  in  only  one  way,  namely,  that 
they  are  reactions  to  "some  harmful  agent  circulating  in  the 
blood,  acting  on  the  axis-cylinder  processes  of  the  neurons  at 
some  point  in  their  course."  Further,  it  seems  clear  to  these 
investigators  that  various  ultimate  causes  may  account  for  the 
reaction  while  it  is  "conceivable  that  the  actual  excitant  of  the 
reaction  is  the  same  in  all  and  a  product  of  body  metabolism 
under  morbid  conditions." 

2.  Direct  cell  reaction  is  due  to  direct  injury  to  the  cell 
and  according  to  Singer  and  Pollock  six  types  are  observed  as 
follows: 

Type  I. — Cell  body  shrunken  and  distorted  with  crenated 
edges  but  in  some  cases  normal  in  size,  more  or  less  uniformly 
staining,  pale  in  color.     Nucleus  rich  in  chromatin. 


PELLAGRA  32 1 

Type  2. — Similar  cell  bodies  with  pale  nucleus  which  may  be 
of  the  same  color  or  lighter  than  that  of  the  cell  body  which 
may  be  reticulated.  Within  the  nucleus  or  nucleolus  are 
granules  staining  a  bluish  green  with  thionin.  In  some  of 
these  the  nucleus  is  lost,  with  or  without  the  nucleolus. 

Type  3. — Shrunken,  uniformly  dark-staining  cell  body  and 
dark  nucleus  sometimes  filling  almost  the  whole  cell. 

Type  4. — Simple  chromatolysis.  Body  normal  or  a  little 
larger.  Nissl  granules  are  scattered  diffusely  throughout,  rare- 
fied and  pale  or  present  only  as  a  fine  dust.  Nucleus  approx- 
imately normal  in  staining  and  position.     Nucleolus  dark. 

Type  5. — Shadow  cells,  a  more  extreme  degree  of  the  same 
type  as  the  last.  Nucleus  absent.  The  outline  of  the  cell 
indistinct. 

Type  6. — Vacuolated  cells.  Nucleus  present.  No  Nissl 
bodies.     The  cell  body  contains  vacuoles. 

The  first  four  of  these  types  of  reaction  are  found  constantly 
in  all  regions  of  the  cortex,  while  Types  5  and  6  .are  found  in  the 
majority  of  cases.  These  changes,  especially  Type  3,  are 
found  in  the  cells  of  the  gray  matter  of  the  cord,  principally  in 
the  posterior  horns. 

That  these  reactions  are  due  to  intoxication  of  the  cells  is 
shown  by  the  satellitosis  which  is  here  present. 

The  following  changes  in  the  neurofibrils  were  found  by 
Singer  and  Pollock: 

(a)  Agglutination. 

(b)  Fragmentation. 

(c)  Loss  of  febrils  (in  small  cells  only  with  one  exception). 

(d)  A  peculiar  encircling  of  the  nucleus  and  pigment  masses 
with  agglutinated  fibrils. 

Pigment  is  found  in  all  types  of  cell  change  as  well  as  in 
normal  staining  cells  in  all  cases,  and  is  especially  marked  in 
the  Betz,  large  pyramidal  and  other  axonal  reacting  cells. 
The  pigment  is  of  various  kinds,  black  staining  with  osmic  acid, 
red  with  scharlach,  and  blue  with  nilblue  sulphate. 

5.  Nerve  Fibers. — Scattered  degeneration  of  radial  fibers  of 
the  cortex  is  shown  by  the  Marchi  method  of  staining.  This 
is  not  seen  in  the  superadiary  or  tangential  fibers. 


322  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Degenerated  fibers  are  seen  in  all  regions  of  the  spinal  cord, 
the  posterior  columns  being  most  involved.  In  the  crossed 
pyramidal  tracts  the  reaction  is  not  more  marked  than  in  the 
other  portions  of  the  cord,  in  fact  is  sometimes  practically 
absent  here. 

Some  degenerated  fibers  are  seen  in  the  anterior  and  posterior 
roots,  and  occasionally  the  number  is  quite  large. 

6.  Amyloid  Bodies  and  Pigment  Granules. — All  eases  of 
pellagra  show  an  excess  of  amyloid  bodies,  beneath  the  epin- 
dyma,  along  the  blood-vessels,  in  the  thickened  glia  of  the 
most  superficial  layers  of  the  cortex,  the  periphery  of  the 
spinal  cord  and  around  the  central  canal.  The  origin  of  these 
bodies  is  not  certain,  but  they  are  found  in  chronic  degenerative 
conditions  such  as  the  senium. 

The  occurrence  of  pigment  granules  of  fatty  and  fibrinoid 
nature  in  the  tissues  and  perivascular  lymph  spaces  is  seen  in 
all  cases. 

By  their  most  exhaustive  study  of  the  pathology  of  the  central 
nervous  system  Singer  and  Pollock  reach  the  following  con- 
clusions: 

1.  The  acute  pellagra  attack  is  accompanied  by  evidence  of 
both  acute  and  more  chronic  intoxication. 

2.  In  common  with  other  intoxicative  conditions,  the  acute 
pellagra  attack  gives  rise  to  a  "central  neuritis"  reaction. 

3.  None  of  the  changes  are  characteristic  of  this  particular 
form  of  intoxication. 

4.  There  is  no  evidence  of  a  local  infection  of  the  nervous 
system  with  microorganisms. 

5.  From  our  cases  it  is  impossible  to  determine  whether  the 
more  chronic  changes  found  in  the  absence  of  a  recent  pellagrous 
exacerbation  belong  to  the  pellagra  picture. 

6.  There  is  no  evidence  to  show  that  chronic  vascular  changes 
are  essential  to  the  picture  of  pellagra. 

Lungs. — No  definite  lesions  of  the  lungs  due  to  pellagra  per 
se  are  found.  This  disease  may  be  found  complicated  with 
many  pathologic  conditions  of  the  lungs,  such  as  pleurisy, 
pneumonia,  edema,  hyperemia  and  emphysema.  It  has  been 
stated  that  pellagra  is  rarely  comphcated  by  phthisis. 


PELLAGRA  323 

Heart. — While  this  organ  frequently  shows  changes  from  the 
normal  such  as  hypertrophy,  atrophy,  hydropericardium  and 
myocardial  softening,  none  of  these  lesions  can  be  ascribed  to 
the  pellagra  itself.  Microscopically  brown  atrophy  and  fatty 
degeneration  are  often  seen. 

Spleen. — The  spleen  of  most  pellagrins  is  atrophied,  although 
it  may  be  found  enlarged  in  some  instances. 

Pancreas. — The  pancreas  is  usually  normal,  but  may  be 
atrophied. 

Kidneys. — These  organs  may  appear  normal,  but  usually 
show  some  pathology,  being  nearly  always  diminished  in  size. 
Chronic  interstitial  nephritis  is  often  seen,  while  fatty  degenera- 
tion of  the  epithelium  of  the  tubules  is  not  uncommon. 

Adrenals. — The  adrenals  are  said  always  to  be  normal. 

Liver. — Atrophy  of  the  liver  is  very  frequent,  it  often  being 
decreased  in  size  to  half  the  normal.  Hypertrophy  may  occur, 
while  fatty  infiltration  is  sometimes  seen. 

Bones. — The  most  marked  changes  in  the  bones  are  seen  in 
the  ribs  which  are  very  frequently  found  to  be  fragile.  Other 
bones  are  at  times  also  fragile. 

The  bones  of  the  calvarium  may  be  thickened  although  some- 
times they  are  thinner  than  normal. 

Muscles. — The  muscular  system  is  usually  atrophied  al- 
though it  may  be  normal  and  even  well  developed.  Fatty 
degeneration  has  been  noted. 


CHAPTER  XX 

CLINICAL  HISTORY  OF  PELLAGRA 

As  may  readily  be  inferred  a  disease  showing  so  varied  and 
marked  pathology  as  pellagra  will  have  a  symptomatology  as 
varied  and  marked.  This  fact  led  to  Lomborso's  famous 
epigram,  "there  is  no  disease;  only  the  diseased."  Neverthe- 
less pellagra  is  a  definite  morbid  entity  and  may  be  differentiated 
from  other  diseases. 

The  clinical  history  of  pellagra  may  be  divided  into  those 
symptoms  referable  to  the  skin,  those  of  the  gastro-intestinal 
tract  and  those  referable  to  the  central  nervous  system.  To 
these  may  be  added  certain  general  signs  and  symptoms. 
Most  pellagrographers  divide  the  clinical  history  of  pellagra  into 
stages,  as  follows:  The  prodromal  stage,  during  which  there 
is  little  deviation  from  the  normal  but  a  general  malaise  and 
vague  undescribable  symptoms;  the  first  stage,  during  which 
the  gastro-intestinal  and  skin  symptoms  are  manifest;  the  second 
stage,  which  is  marked  by  the  nervous  and  mental  manifesta- 
tions; and  the  third  or  terminal  stage,  in  which  cachexia  is  seen. 

While  this  artificial  and  arbitrary  classification  of  symptoms 
is  in  some  respects  convenient  for  ease  of  description,  pellagra 
does  not  by  any  means  always  follow  such  a  regular  course, 
nor  can  the  stages  definitely  be  separated  by  a  sharp  Kne  of 
demarcation.  Further,  no  definite  period  of  time  can  be  named 
as  covering  the  course  of  the  disease. 

Pellagra  is  essentially  a  chronic  disease  and  as  stated  above 
is  marked  by  more  or  less  seasonal  periodicity,  exacerbations 
alternating  with  periods  of  remission.  The  average  pellagrin 
will  give  a  history  of  having  "felt  bad"  for  a  varying  time 
previous  to  the  active  outbreak  of  the  disease.  The  first 
actual  symptoms  noted  are  usually  those  of  the  gastro-intestinal 
tract,  red  and  coated  tongue,  dyspepsia  with  flatulence  and 
distention,  occasionally  abdominal  pain,  and  diarrhea.  The 
324 


PELLAGRA 


325 


latter  symptom  may  be  replaced  by  constipation.  Vertigo 
and  headache  are  frequent  and  the  deep  tendon  reflexes  may 
be  exaggerated. 

The  skin  manifestations  usually  occur  early  and  as  a  rule 
select  the  exposed  surfaces  of  the  body.  They  may  be  the 
first  symptoms  noted. 

Sometimes  at  a  very  early  date  there  are  psychic  disturbances, 
usually  of  a  mild  character,  although  as  a  rule  they  occur  later 
in  the  course  of  the  disease.     The  first  outbreak  may  be  mild  in 


-  ^^^'' 


P^ig.   70. — Showing  wrinkled  condition  of  skin  following  eruption. 

nature  and  pass  almost  unnoticed,  to  recur  at  a  variable  time, 
usually  the  following  spring  in  an  exaggerated  form  or  the  first 
outbreak  may  be  severe  in  type. 

The  skin  eruption  will  be  more  marked  and  the  gastro-in- 
testinal  symptoms  more  severe,  while  the  nervous  and  mental 
manifestations  will  take  on  a  more  serious  aspect. 

The  disturbances  of  motility  are  usually  marked,  such  as 
muscular  weakness,  and  even  paralysis. 

The  psychic  nianifestations  are  most  variable,  ranging  from 
the  deepest  depression  to  great  excitability. 

There  may  again  be  periods  of  remission  followed  by  exacer- 
bations, each  one  usually  becoming  more  severe  until  finally 


326 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


there  is  a  most  distressing  picture  of  cachexia,   dementia  and 
paralysis  and  the  chapter  is  closed  with  death. 

Incubation  Period. — It  seems  paradoxical  to  attempt  to  as- 
sign an  incubation  period  to  a  disease  about  the  etiology  of 
which  so  little  is  known,  and  it  is  a  fact  that  the  majority  of 
writers  who  have  so  assigned  an  incubation  period  have  done 
so  on  the  assumption  that  the  cause  of  the  disease  is  known. 


Fig.   71. — Slight  dermatitis  of  feet  and  ankles  of  negress. 

Thus  Sandwith,^"'  who  so  religiously  holds  to  the  spoiled- 
corn  theory  of  the  etiology  of  pellagra,  considers  the  incuba- 
tion period  to  be  from  nine  to  twelve  months  in  length.  He 
bases  his  opinion  on  the  fact  that  corn  is  harvested  in  Egypt 
in  November  and  December,  while  in  the  majority  of  patients 
the  disease  begins  in  January.  From  these  facts  he  assumes 
that  the  corn  could  not  have  become  sufficiently  spoiled  in 
this  time  to  cause  the  disease,  and  he  therefore  incriminates  the 
crop  of  the  previous  season. 

Merk,'^-  who  also  believes  in  the  corn  theory,  states  that  the 
incubation  period  is  from  seven  to  nine  months. 


PELLAGRA 


327 


Sambon,'--  the  author  of  theSimuhum  theory,  is  of  the  opinion 
that  the  incubation  period  is  short,  and  of  course  bases  his 
opinion  upon  the  assumption  that  the  bite  of  the  insect  is 
necessary  to  the  development  of  the  disease.  He  states  that 
he  has  seen  pellagra  in  infants  of  five  months  of  age  who  have 
not  been  taken  to  the  fields  until  two  or  three  weeks  previous 
to  the  appearance  of  the  eruption;  he  therefore  fixes  the  period 
of  incubation  at  about  two  weeks. 

While  the  above-mentioned  pellagragraphers  are  undoubtedly 


Typic  eruption  on  backs  of  hands  of  gir!  of  sixteen. 


convinced  of  the  correctness  of  their  views,  it  seems  to  us  that 
all  discussion  as  to  the  incubation  period  of  pellagra  is  irrelevant 
until  the  etiologic  factor  of  the  disease  has  been  scientifically 
demonstrated. 

Skin  S3Tnptoins. — While  as  stated  above  the  symptoms  of 
the  gastro-intestinal  tract  are  usually  the  first  to  be  observed,  it 
often  occurs  that  the  skin  eruption  develops  first.  The  most 
frequent  time  of  the  first  occurrence  of  the  skin  lesions  is  in  the 
spring,  but  they  may  develop  first  in  the  fall.  Recurrences  in 
the  fall  following  a  spring  eruption  may  occur. 

These  manifestations  are  usually  spoken  of  as  an  erythema. 


328 


ENDEMIC   DISEASES    OF    THE    SOUTHERN    STATES 


but,  as  Fox^--  has  pointed  out,  the  erythema  with  which  the 
lesions  usually  begin  is  of  minor  importance  owing   to  the 


Fig.  74. — Extensive  and  severe  eruption  on  arms.    . 

comparatively  short  time  it  lasts,  and  dermatitis  would  be  a 
more  appropriate  term. 


PELLAGRA 


329 


Fig.  75. — Rather  unusual  eruption  affecting  but  small  portion  of  backs  of  hands. 


Fig.  76. — Typic  eruption  on  backs  of  hands  and  arms. 


33° 


ENDEMIC   DISEASES    OF    THE    SOUTHERN    STATES 


The  most  frequent  location  of  the  skin  lesions  of  pellagra  is 
the  backs  of  the  hands.  The  palms  are  rarely  affected  and  the 
last  two  phalanges  of  the  fingers  sometimes  are  not  involved, 
while  the  nails  are  never  attacked.  The  eruption  may  extend 
to  the  wrist  and  for  some  distance  up  the  extensor  surface  of 
the  forearm.     Occasionally  the  lesion  may  completely  encircle 

r 


Fig.  77. — Extensive  eruption  of  face  and  backs  of  hands, 
parallel  to  border  of  dermatitis. 


Note  white  band 


the  forearm.  The  line  of  demarcation  between  the  normal  and 
diseased  piortion  of  the  skin  is  usually  quite  pronounced  and 
the  so-called  "pellagrous  glove"  is  not  infrequently  seen. 

A  condition  which  we  have  observed  in  one  case  and  have 
not  seen  described  elsewhere,  is  a  distinct  narrow  white  Hne  in 
the  dermatitis  about  a  half  inch  from  the  line  of  demarcation 
between  the  diseased  and  sound  skin.  This  condition  is 
shown  in  Fig.  77. 

Probably  the  most  characteristic  feature  of  the  skin  mani- 


PELLAGRA 


331 


festations  of  pellagra  is  the  symmetry.  This  condition  is 
most  constant  and  may  be  considered  almost  pathognomonic, 
although  the  lesions  on  both  sides  of  the  body  need  not  develop 
simultaneously. 

The  lesions  seem  to  prefer  the  exposed  surfaces  of  the  body 


Fig.  78. — "  Butterfly  "  eruption  on  face  of  child  two  years  old. 

and  are  found  very  frequently  on  the  face,  back  of  the  neck, 
chest  and  dorsal  surfaces  of  the  feet.  The  attacking  of  the 
exposed  surfaces  is  by  no  means  constant,  as  the  lesions  are 
frequently  found  on  the  covered  portions  of  the  body. 

The  upper  arms,  elbows,  knees  and  thighs  are  often  the  seat 
of  the  dermatitis.     Sometimes  the  external  genitalia,  the  vulva 


332 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


in  women  and  the  scrotum  in  men,  are  involved  and  the 
eruption  has  been  noted  on  the  buttocks  extending  from 
one  cheek  to  the  other,  while  complete  involvement  of  the  in- 
tegument of  the  body  is  occasionally  observed. 

It  is  rare  to  see  lesions  on  other  parts  of  the  body  when  the 
hands  are  not  involved. 

The  lesions  on  the  backs  of  the  hands  may  cover  the  entire 
surface  or  they  may  occur  in  spots  4  or  5  cm.  in  diameter  with 


<-f- 


Fig.  79. — Desquamation  of  skin  of  backs  of  hands. 

areas  of  normal  skin  between.  The  spots  may  become  confluent 
or  they  may  remain  separate. 

On  the  face  the  lesions  may  also  occur  in  spots,  the  most 
frequent  location  being  the  alse  of  the  nose,  after  which  in 
the  order  of  frequency  the  lesions  occur  on  the  forehead,  cheeks 
and  chin.  The  lips  usually  escape  as  do  the  ears  and  eyehds. 
The  face  may  be  the  seat  of  a  diffuse  eruption  known  as  the 
pellagrous  mask. 

The  lesions  of  the  neck  are  very  variable  in  character.  The 
back  of  the  neck  alone  may  be  involved  or  there  may  be  a 
complete  circle  of  the  eruption  corresponding  to  the  exposed 
portion,  such  as  in  women  accustomed  to  low-necked  clothing 
or  in  men  who  leave  the  shirt  unfastened  at  the  neck.     The 


PELLAGRA  333 

so-called  "Casal  collar"  is  described  by  Mark  as  beginning  on 
the  back  of  the  neck  a  little  below  the  margin  of  the  hair  and 


Fig.  80. — Extensive  dermatitis  of  arms  and  feet.     (Dr.  T.  E.  Sanders.) 

extending  around  the  neck  parallel  to  the  lower  jaw  and  several 
finger-breadths  from  it.  The  two  lines  meet  on  a  level  with 
the  larynx  above.     The  lower  border  is  said  to  begin  a  little  be- 


334 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


low  the  vertebra  prominens,  pass  around  the  root  of  the  neck  on 

either  side  and  unite  over  the  upper  part  of  the  manubrium. 

The  pellagrous  eruption  of  the  feet  is  of  rather  frequent  oc- 


Fig.  8i. — Back  of  same  patient  as  shown  in  Fig.  80. 

currence.  The  dorsal  surfaces  alone  are  usually  involved,  al- 
though rarely  the  soles  of  the  feet  are  affected.  The  line  of 
demarcation  is  usually  in  the  region  of  the  malleolus,  although 
the  lesion  may  pass  on  up   the  ankle.     While  the  toes  are 


PELLAGRA 


335 


generally  not  involved  there  are  exceptions,  the  great  toe  being 
most  frequently  the  seat  of  the  eruption. 

While  the  pellagrous  dermatitis  of  the  feet  is  most  frequent 
in  those  who  do  not  wear  shoes  and  stockings,  it  is  often  noted 
in  those  who  do  and  even  in  those  who  are  bedridden.  There 
is  nothing  especially  characteristic  about  the  skin  lesions  of  the 


Fig.  82. — Casal's  collar  in  negress. 

upper  arms,  elbows,  knees  and  thighs  except  the  symmetry. 
It  is  of  importance  not  to  confuse  the  simple  roughening  of  the 
skin  over  the  knees  and  elbows  with  the  pellagrous  eruption. 

Lesions  of  the  external  genitalia  are  not  of  rare  occurrence 
and  should  not  be  overlooked.  Dermatitis  in  the  anal  region, 
especially  in  patients  with  diarrhea,  is  sometimes  observed. 

It  is  customary  to  divide  the  skin  eruptions  into  "wet"  and 
"dry"  lesions  depending  on  whether  or  not  bullse  are  formed. 

As  stated  above,  the  usual  beginning  of  the  skin  manifesta- 


336 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


tions  very  markedly  resembles  a  severe  sunburn  and  often  is 
indistinguishable  from  it. 

It  is  usually,  however,  darker  in  color  without  the  usual 
pinkish  hue  of  the  erythema  of  sunburn.  In  dark-skinned 
individuals,  especially  the  negro,  the  color  of  the  eruption  may 
take  a  grayish  hue,  while  the  normal  pigment  of  the  part  deepens 


Fig.   83. — Extensive  dermatitis  on  back. 

in  color.  The  skin  of  the  affected  area  is  generally  slightly 
puffed  and  a  slight  burning  sensation  is  complained  of,  while 
there  is  some  pruritis.  At  first  the  color  disappears  on  pressure 
but  returns  when  the  pressure  is  removed.  Later  this  phe- 
nomenon is  not  observed. 

The  color  of  the  eruption  gradually  deepens  and  when  at  its 
height  is  a  reddish  brown  or  chocolate  shade,  this  depending 
upon  the  color  scheme  of  the  individual.     The  first  eruptive 


PELLAGRA 


337 


symptoms  may  disappear  in  two  or  three  weeks  with  exfoha- 
tion  of  the  epidermis  usually  in  light  scales,  although  exfolia- 
tion may  occur  in  large  flakes.  The  area  is  left  pigmented 
according  to  the  severity  of  the  lesion. 

As  stated  above,  the  pellagrous  eruption  may  begin  not  as  an 
erythema  but  with  discrete  maculae  which  may  persist  for  two 
to  three  weeks  and  then  disappear. 


■Typic  eruption  on  elbows. 


The  so-called  "wet"  pellagrous  eruption,  as  distinguished 
from  the  "dry"  form  just  described,  begins  with  the  typical 
erythema,  upon  which  in  a  short  time  are  superimposed  vesicu- 
lar or  bullous  lesions  of  greater  or  less  extent.  These  lesions 
are  always  monolocular,  and  the'  contents  which  in  the  be- 
ginning is  sterile  fills  the  space  without,  leaving  the  covering 
epidermis  in  a  flaccid  condition. 


338 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


The  bullae  are  not  found  in  all  regions  where  the  dry  derma- 
titis is  found,  but  are  located  chiefly  on  the  backs  of  the  hands, 
the  neck  and  occasionally  on  the  feet  and  legs. 

Secondary  infection  with  pyogenic  organisms  is  not  an  in- 
frequent occurrence,  the  bleb  being  converted  into  an  abscess. 
Following  this  there  is  edema  of  the  underlying  skin  and  that 
adjacent,  with  more  or  less  inflammatory  reaction. 


Fig.  85. — Typic  dry  eruption  on  liands  and  forearms. 

The  bullae  may  be  ruptured  by  some  mechanical  means  and 
the  lesions  become  granulating  wounds,  or  they  may  gradually 
dry  up,  the  covering  being  converted  into  a  fine  crust  of  a 
yellowish-green  color  beneath  which  the  epidermis  gradually 
becomes  regenerated. 

Skin  lesions  developing  from  the  original  erythema  in  which 
fissures  are  developed  have  been  noted.     These  at  first  are 


PELLAGRA  339 

confined  to  the  corium,  but  later  invade  the  deeper  layers. 
This  type  of  lesion  may  heal,  leaving  little  or  no  trace  if  infection 
does  not  occur.  In  the  event  of  the  latter  a  granulating  wound 
develops,  which  is  followed  by  cicatrization.  Not  infrequently, 
when  thi,s  class  of  lesion  develops,  blebs  also  are  seen. 

Desquamation  without  erythema  is  sometimes  seen,  but  this 
is  certainly  rare. 

Pustular  lesions  have  been  reported,  especially  on  the  face. 
The  pustules  vary  from  the  size  of  a  millet  seed  to  that  of  a 
pea  and  are  said  to  occur  either  without  the  erythema  or  com- 
plicating it.  We  have  never  seen  a  case  of  pustular  pellagra 
except  one  in  which  the  bullous  lesions  had  become  infected. 

Pellagra  hemorrhagica  is  another  rare  form  of  the  skin  lesions. 
It  occurs  as  small  hemorrhagic  areas  beneath  the  skin  and  is 
seen  on  the  backs  of  the  hands,  arms,  face  and  neck. 

Pellagra  sine  pellagra,  the  disease  without  the  skin  manifes- 
tations, has  been  described.  This  condition  will  be  discussed 
more  fvilly  later. 

The  eruption  of  pellagra  begins  rather  suddenly,  reaches  its 
maximum  intensity  in  a  variable  time  from  several  days  to  a 
few  weeks,  and  retrogresses  gradually,  requiring  from  a  few 
weeks  to  several  months  to  disappear.  After  the  first  attack 
the  skin  remains  pigmented  for  some  time.  Following  attacks 
leave  the  skin  much  thickened,  roughened,  hard  and  pigmented. 
The  color  is  a  peculiar  bronze  or  yellowish  green.  After  several 
attacks  the  skin  may  become  atrophied  and  lose  its  elasticity 
almost  entirely.     White  spots  are  also  often  seen. 

Gastro-intestinal  Symptoms. — The  symptoms  referable  to 
the  gastro-intestinal  tract  are  usually,  as  stated  above,  the 
first  to  appear  and  undoubtedly  they  are  the  most  important. 
Not  only  are  there  many  symptoms  present  due  to  the  actual 
demonstrable  organic  changes,  but  usually  there  are  also  many 
functional  symptoms  observed. 

Stomatitis  of  varying  degree  with  glossitis  is  one  of  the  most 
constant  symptoms  of  pellagra.  Often  this  condition  is  so 
mild  as  to  pass  unrecognized  by  the  patient,  and  is  detected 
only  after  a  careful  and  painstaking  examination  by  the 
physician. 


340  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

The  tongue  is  usually-  denuded  of  epithelium  and  is  always 
red,  especially  along  the  edges.  It  may  be  thick  and  beefy  or 
it  may  present  a  pointed  appearance.  Along  the  edges  there 
may  be  ulcers. 

The  outer  borders  of  the  Ups  are  dry,  and  in  severe  cases 
present  a  more  or  less  cyanotic  appearance.  The  inner  borders 
of  the  lips  in  severe  cases  are  tender,  raw  and  swollen.  Black 
spots  may  be  noted. 

The  stomatitis  and  glossitis  may  be  so  severe  that  the  tongue 
cannot  be  protruded  and  eating  and  swallowing  may  be  ac- 
complished only  with  the  greatest  difficulty,  while  taking  into 
the  mouth  of  even  weak  acids  is  accompanied  with  considerable 
burning.  Most  pellagrins  complain  of  a  "bad  taste"  in  the 
mouth.  The  breath  is  usually  very  foul  and  saliva  may  flow 
so  freely  that  the  patient  cannot  speak.  The  teeth  are  not 
always  affected,  but  pyorrhea  is  not  uncommon.  There  is 
sometimes  a  bilateral,  non-suppurating,  painless  parotitis. 
The  other  salivary  glands  are  usually  normal  in  size. 

There  is  a  sensation  of  heat  in  the  mouth,  throat  and  stomach; 
in  fact,  these  symptoms  may  precede  any  noticeable  pathologic 
change.  This  sensation  of  heat  is  undoubtedly  due,  in  part  at 
least,  to  the  pathologic  changes,  but  may  also  be  caused  by  a 
neurosis. 

The  appetite  is  usually  diminished,  although  some  patients 
are  loud  in  their  clamor  for  food.  Some  suffer  from  thirst, 
while  others  will  only  drink  when  forced  to. 

The  principle  gastric  symptoms  are  those  of  gastritis,  dis- 
tention, belching,  gastralgia,  nausea  and  rarely  vomiting  except 
in  advanced  cases. 

It  not  infrequently  occurs  that  a  patient  consults  a  physician 
for  more  or  less  vague  indefinite  gastric  symptoms  and  is 
treated  for  the  same  for  some  time,  when  the  typical  stomatitis 
or  skin  eruption  develops  and  the  true  nature  of  the  condition 
is  revealed. 

The  distention  and  belching  are  often  most  severe  causing 
the  patient  great  discomfort. 

Gastralgia  varies  from  the  vague  indefinite  "hunger  pains'' 
to  most  severe  epigastric  pains  and  bear  no  relation  to  the  in- 


PELLAGRA  34I 

take  of  food.  These  are  often  mistaken  for  the  gastric  crises 
of  tabes  dorsalis,  especially  in  the  later  course  of  the  disease 
when  the  nervous  system  is  involved.  There  is  usually  more 
or  less  epigastric  tenderness. 

The  gastralgia  is  usually  intermittent  even  during  the  acute 
attack,  but  often  persists  after  the  dermatitis  and  other 
symptoms  have  disappeared,  in  fact,  it  may  last  in  a  more  or 
less  severe  form  until  another  acute  attack  occurs. 

The  nausea  of  pellagra  is  generally  not  marked.  It  may  occur 
early  in  the  disease,  but  more  frequently  as  a  later  manifesta- 
tion. Sandwith^"'  states  that  vomiting  does  not  occur. 
Niles'"^  says  that  in  200  cases  vomiting  was  seen  less  than 
twenty  times.  Other  observers  find  it  a  rather  frequent  ac- 
companiment to  the  final  stages  of  the  disease.  We  have 
recently  had  a  case  in  which  vomiting  was  an  early  and  ob- 
stinate symptom. 

Roberts^""  is  of  the  opinion  that  the  burning  pains  are  re- 
ferred, having  a  common  origin  with  the  burning  sensations  of 
the  hands  and  feet,  that  they  do  not  arise  from  a  gastric  con- 
dition, "but  are  rather  due  to  cord  involvements  and  impulses 
reflected  through  the  sympathetic  ganglia." 

With  these  views  we  cannot  agree.  In  the  first  place  these 
symptoms  occur  in  the  vast  majority  of  cases  long  before  any 
demonstrable  nervous  symptoms  exist;  and  in  the  second  place, 
the  pathologic  anatomy  of  the  stomach  in  pellagra  is  usually 
sufficient  to  account  for  the  gastric  symptoms. 

One  of  the  most  frequent  symptoms,  and  also  one  of  the  most 
difficult  to  control  is  diarrhea.  However,  instead  of  diarrhea 
there  may  be  constipation,  and  not  infrequently  the  two  symp- 
toms alternate  one  with  the  other. 

Various  investigators  report  that  from  85  to  100  per  cent,  of 
their  cases  show  diarrhea  at  one  time  or  another.  The  time 
of  the  appearance  of  the  diarrhea  is  somewhat  variable.  Very 
often  it  is  the  first  symptom  to  be  noted;  however,  it  is  not  at 
all  unusual  for  the  three  symptoms,  diarrhea,  stomatitis,  and 
dermatitis  to  appear  at  nearly  the  same  time. 

The  development  of  the  diarrhea  is  nearly  always  gradual,  and 
its  disappearance  with  the  recession  of  the  disease  is  also  gradual. 


342  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

In  the  beginning  the  diarrhea  is  usually  of  a  spasmodic 
character  and  is  accompanied  with  more  or  less  pain  and  griping. 
The  stool  is  dysenteric  and  muco-sanguinolent  in  character. 

It  is  hard  for  the  patient  to  control  the  sphincter  and  often 
his  clothing  may  become  soiled.  In  the  mild  cases  the  diarrhea 
as  described  gradually  improves  with  the  other  symptoms. 
In  the  severe  cases  it  becomes  worse.  The  stools  assume  a 
more  watery  appearance,  and  are  of  more  frequent  occurrence. 
Neither  rest  nor  food  influence  the  condition,  there  being  as 
many  bowel  movements  at  night  as  during  the  day.  There 
may  be  distention  and  paralysis  of  the  intestines. 

Opium  even  in  large  doses  has  little  or  no  effect,  and  the 
condition  persists  until  a  remission  occurs  or  death  ensues.  In 
the  severe  cases  the  stool  may  be  almost  watery  in  consistence, 
of  a  hght  gray  color,  often  tinged  with  blood,  and  is  usually 
very  irritating  to  the  parts. 

The  odor  of  the  pellagrous  stool  is  most  characteristic,  some 
writers  even  going  so  far  as  to  state  that  a  diagnosis  may  be 
made  upon  this  feature  alone. 

Diarrhea  is  frequently  the  only  symptom  to  appear  in  the 
fall  after  an  acute  pellagrous  attack  the  previous  spring,  and 
this  symptom  is  a  rather  good  index  to  the  severity  of  the 
disease;  the  less  severe  the  diarrhea  the  more  mild  the  case  and 
vice  versa.  Often  the  cases  which  show  constipation  run  a 
mild  course. 

Should  the  patient  become  convalescent  for  a  long  time  his 
appetite  is  variable,  indigestion  is  usually  brought  on  by  slight 
indiscretions  in  diet,  the  flatulence  and  eructions  are  rather 
frequent. 

Nervous  Symptoms. — The  nervous  symptoms  of  pellagra 
as  usually  described  are  most  varied,  and  by  most  pellagra- 
graphers  great  importance  is  attached  to  them. 

Thus  Sandwith^-'  states  that  in  the  acute  stage  there  is 
usually  pain  in  the  back,  which  may  be  so  severe  as  to  compel 
the  patient  to  walk  with  body  arched.  The  pain  is  elicited 
on  both  sides  of  the  vertebral  column  by  pressure  over  the 
spinal  nerves.  These  symptoms  generally  disappear  if  the 
patient  remains  in  the  hospital  for  a  month. 


PELLAGRA  343 

The  lower  tendon  reflexes  are  found  disturbed  in  the  majority 
of  cases.  According  to  Sandwith  46  per  cent,  show  marked 
exaggeration,  29  per  cent,  slightly  increased,  9  per  cent,  dimin- 
ished, 14  per  cent,  absent  and  2  per  cent,  normal. 

While  these  reflexes  are  usually  on  both  sides  they  may  be 
asymmetrical.  Ankle  clonus  is  occasionally  noted.  Tremor  of 
the  fingers  and  of  the  tongue  are  often  observed  rather  early 
in  the  disease,  while  in  the  later  stage  tremors  are  usually  most 
marked. 

There  is  no  typical  "gait"  in  pellagra;  nevertheless  there 
may  be  a  spastic  gait.  A  positive  Romberg  is  often  noted. 
Vertigo  is  a  frequent  symptom,  and  usually  occurs  when  the 
patient  is  standing,  but  may  develop  when  the  patient  is  in 
bed. 

Singer^^^  has  pointed  out  that  there  are  none  of  these  symp- 
toms but  may  be  observed  in  other  severe  intoxicative  condi- 
tions such  as  tuberculosis.  He  further  states  that  "faulty 
nervous  organization  seems  for  some  reason  to  be  associated 
with  a  predisposition  to  pellagra." 

Singer  gives  in  detail  the  history  of  the  only  case  which  came 
under  his  observation  in  which  there  were  evidences  of  chronic 
structural  change  in  the  nervous  system.  In  this  case  there 
were  noted  occasional  brief  attacks  of  loss  of  power  in  the  lower 
extremities  following  an  attack  of  pellagra.  These  attacks 
lasted  from  fifteen  to  twenty  minutes  followed  by  apparently 
complete  recovery.  Following  a  second  attack  of  pellagra 
there  was  atrophy  of  the  small  muscles  of  the  hands  and  spastic 
paraplegia  of  gradual  development. 

In  spite  of  these  manifestations  Singer  is  of  the  opinion  that 
the  pellagra  merely  acted  as  a  precipitating  force  and  was  not 
the  cause  per  se  of  the  nervous  symptoms. 

Mental  Symptoms. — For  a  long  time  it  has  been  recognized 
that  pellagra  is  very  frequently  accompanied  by  mental  dis- 
orders, and  of  later  years  some  investigators  have  even  gone 
so  far  as  to  consider  the  involvement  of  the  central  nervous 
system  (both  nervous  and  mental  symptoms)  as  the  principle 
evidence  of  this  disease.  Others  ascribe  to  it  the  cause  of 
mental  derangement  and  describe  a  pellagrous  insanity. 


344  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

This  insanity  according  to  most  writers  takes  various  forms; 
thus  Marie^"*  states  that  the  most  frequent  form  of  psychosis 
in  pellagra  is  mental  confusion,  with  depressive  states  and  with 
dehrium,  while  Sorbets,  according  to  Babcock,-^^  says,  "For 
ahenists,  hallucinations  are  the  chief  characteristics,  the  pathog- 
nomonic phenomenon  of  pellagrous  insanity." 

Green  as  quoted  by  Roberts^""  states  that  at  the  present  time 
it  is  impossible  to  recognize  a  pellagrous  insanity  as  an  entity, 
and  temporarily  it  is  best  to  classify  the  mental  condition  as  the 
"psychosis  accompanying  pellagra"  and  to  subdivide  the  groups 
into  types  according  to  the  symptoms.  He  therefore  describes 
the  following  types:  infective  exhaustive,  manic  depressive, 
dementia  praecox,  general  paralysis,  senile,  involutional  melan- 
cholia and  unclassified. 

Gregor^^''  has  distinguished  between  the  abnormal  mental 
pictures  directly  attributable  to  pellagra,  that  is,  caused  by 
change  in  the  brain  due  to  the  presence  of  the  pellagra  toxin 
and  those  which  are  secondary. 

Singer^''''  has  proposed  the  following  classification  of  the 
types  of  mental  disorder  associated  with  pellagra. 

Group  I.  Disorders  directly  due  to  the  pellagra  toxin  (or 
toxins) . 

1.  Symptomatic  depressions. 

2.  Delirious  pictures. 

Group  II.  Disorders  based  on  peculiarities  in  the  personal 
make-up,  the  attack  of  insanity  being  precipitated  by  pellagra. 

1.  Manic  depressive  disorders. 

2.  Hysteria. 

3-  Psychasthenia. 

4.  Dementia  prsecox. 

5.  Paranoic  developments. 

Group  III.  Disorders  due  to  definite  brain  changes  with 
pellagra  merely  as  a  complication. 

1.  Arteriosclerosis  dementia. 

2.  Senile  dementia. 

3.  Presenile  psychoses. 

4.  General  paralysis  of  the  insane. 

Singer  considers  the  relation  of  pellagra  to  mental  disturb- 


PELLAGRA  345 

ance  the  same  as  that  of  other  general  diseases,  and  that  while 
similar  pictures  as  observed  in  pellagra  are  encountered  in 
t3T)hoid  fever,  yet  a  separate  grouping  is  not  made. 

There  may  be  cases  in  which  the  mental  condition,  such  as 
delirium,  is  due  to  the  action  of  toxins  of  the  disease  on  the 
brain,  or  there  may  be  a  picture  of  dementia  praecox  or  manic- 
depressive  insanity  which  runs  a  similar  course  to  those  cases 
in  which  there  is  no  infection.  If  pellagra  develops  in  a  de- 
mentia prsecox  predisposed  individual  it  will  be  the  "lalt  straw" 
to  bring  on  the  symptoms  of  the  mental  disease.  Another 
view  of  the  matter  is  taken  by  Singer,  which  is  that  the  relation 
of  the  functional  psychoses  (including  dementia  precox)  and 
pellagra  is  the  reverse  of  the  usually  accepted  theory.  That 
instead  of  the  pellagra  being  the  cause  of  the  psychosis,  it  may 
be  that  the  psychosis  or  "the  poor  adaptability  and  peculiarity 
of  make-up,"  predisposes  the  individual  to  pellagra.  It  is 
certainly  a  fact  that  pellagra  very  frequently  develops  among 
the  chronic  insane. 

Singer  admits  that  "the  relation  of  pellagra  to  the  psychoses 
due  to  more  definite  brain  disease  or  degeneration  such  as  the 
presenile,  senile  and  arteriosclerotic  dementias,  is  a  somewhat 
different  question.  He  states  that  there  is  no  doubt  of  the 
occurrence  of  pellagra  with  these  conditions,  and  that  they 
may  predispose  the  body  to  pellagra  or  that  the  pellagra  might 
favor  the  early  development  of  involution  change  or  even 
provoke  arterial  degeneration. 

While  admitting  the  occurrence  of  pellagra  with  paresis. 
Singer  cannot  agree  that  there  is  a  type  of  mental  disturbance 
in  pellagra  comparable  with  the  general  paralysis  of  the  in- 
sane. The  picture  which  is  generally  so  described  is  that  of 
general  intoxication  with  central  and  possibly  peripheral  neur- 
itis, and  much  more  resembles  the  severe  toxic  forms  of  the 
infective  fevers,  such  as  typhoid,  than  it  resembles  paresis. 

In  describing  the  symptomatic  depressions  which  occur  in 
pellagra,  Singer  states  that  they  are  by  far  the  most  frequent 
if  cases  outside  hospitals  for  the  insane  are  included.  There  is 
a  marked  depression,  although  there  need  be  no  objective  signs 
of  fatigue.     The  most  striking  characteristic  of  this  class  of 


346  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

cases  is  that  the  mental  symptoms  are  severe  or  mild  as  the 
other  symptoms  progress  or  recede.  There  is  more  or  less 
hopeless  sadness,  thinking  is  difficult  and  general  lowering  of 
tone  exists  while  apprehension  without  definite  fear  is  often 
observed.  This  may  be  expressed  by  the  patient  by  words  or 
by  restlessness. 

The  delirium  sometimes  found  in  pellagra,  Singer  says,  in  the 
vast  majority  of  cases,  is  the  result  of  intoxication  of  the  brain 
causing' changes  in  the  functional  activity  involving  the  high- 
est cerebral  levels.  All  degrees  are  met  with  in  the  mild  cases; 
there  are  short  periods  of  clouding  of  consciousness,  while  in  the 
intervals  the  mind  may  be  practically  clear,  yet  with  depression 
manifest.  There  is  nothing  to  distinguish  these  conditions 
from  those  found  in  other  intoxications,  such  as  in  typhoid. 

In  pellagra,  as  with  other  conditions,  these  manifestations 
probably  depend  upon  two  factors,  viz.,  the  virulence  of  the 
toxin,  and  the  ability  of  the  individual  to  resist  the  poison. 
The  relative  frequency  of  delirium  in  pellagra  may  be  due  to 
the  extreme  virulence  of  the  pellagra  toxin  or  that  the  indi- 
viduals who  contract  pellagra  are  of  poor  nervous  organization. 

The  mental  pictures  of  pellagra  which  are  due  to  the  person- 
ality of  the  individual,  manic-depressive,  dementia  praecox, 
etc.,  are  in  no  way  distinguishable  from  those  conditions  in 
which  pellagra  is  not  present.  There  may  be  some  delirium  due 
to  the  intoxication  which  will  make  the  diagnosis  of  the  type 
more  difficult,  but  this  delirium  will  run  a  course  parallel  to 
the  other  symptoms  of  the  pellagra. 

The  frequency  of  mental  disorders  in  pellagra  is  the  subject 
of  some  differences  in  opinion.  Wood-'''  states  that  the 
"probable  outcome  of  the  ordinary  types  of  pellagra  will  be 
insanity." 

Grimm-'-  found  7.5  per  cent,  of  1,436  cases  were  insane. 

Roberts'""  states  that  it  has  been  estimated  that  10  per  cent, 
of  the  pellagrins  in  Italy  are  insane,  and  considers  that  figure 
much  too  high  for  this  country;  in  fact  that  5  per  cent,  would 
be  nearer. 

In  regard  to  the  various  "t3rpes"  of  mental  change  found  in 
pellagrins.  Green's'""  table  is  as  follows: 


PELLAGRA 


347 


Infective  exhaustive 30 

Manic-depressive 9 

Dementia  prsecox 9 

General  paralysis 2 

Senile 3 

Involution  melancholia 2 

Unclassified 5 


Total. 


60 


Of  the  cases  reported  by  Singer^  ^^  the  following  table  shows 
the  number  and  percentage  of  types: 


Types  or  Mental  Disorders 

IN    A 

Series  oe  Pellagrins 

Thirty-four 
unselected 

the  author 

One  hundred 
and    thirty 
unselected 

cases  seen  by 

Total 

unselected 

cases 

Eighteen 

hospital  cases 

selected  for 

severity 

No.  of 

Per 
cent. 

No.  of 

Per 
cent. 

No.  of 

Per 
cent. 

No.  of 

Per 
cent. 

Group  I: 
Symptomatic  depression. .  . 
Delirious  pictures 

Group  II: 
Manic-depressive  disorders 

Hysterical  disorders 

Dementia  praecox  disorders 

Group  III: 
Arteriosclerotic  dementia . . 

Presenile  psychoses 

Senile  dementia 

9 

2 

0 

I 
0 

0 

I 
0 

26.5 
5-9 

0.0 

0.0 

0.0 
3-0 
0.0 

41 
10 

0 
0 

I 

0 
0 

31-5 

7-7 

0.0 
0.0 
0.8 

0.0 
0.0 
0.0 

5° 
12 

0 

I 
I 

0 

I 
0 

30-5 
7-3 

0.0 
0.6 
0.6 

0.0 
0.6 
0.0 

10 

2 

I 
0 
l(?) 

I 
0 

I 

S5-S 
II .  I 

5-5 
0.0 

5S 

S-5 
0.0 

S-5 

The  following  table  shows  the  mental  condition  of  the  ninety- 
one  cases  seen  by  one  of  us  at  the  Arkansas  State  Hospital  for 
Nervous  Diseases: 

Intoxication  psychosis 55 

Dementia  praecox 20 

Inbecility 5 

Epilepsy 3 

Senility 3 

Manic-depressive 2 

Paranoia i 

Arteriosclerosis i 

Paretic i 

Total 91 


348  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Special  Senses. — ^Eye. — While  the  eyes  of  pellagrins  are 
rarely  normal  there  are,  with  possibly  one  exception,  no  pathog- 
nomonic findings  in  the  eyes  in  this  condition.  This  exception 
is  one  reported  by  Whaley,-*^  who  states  that  as  his  number  of 
cases  is  small  (thirty-five)  he  wound  not  like  to  be  too  san- 
guine about  its  being  pathognomonic.  He  further  states  that 
Lombroso  found  it.  The  symptom  as  described  by  Whaley 
"appears  as  if  the  retina;  were  thickened  and  gives  the  fundus 
reflex  a  peculiar  indistinct  yellowish  color,  and  is  not  so  pro- 
nounced as  the  senile  reflex." 

The  pellagrous  eruption  may  appear  on  the  eyelids  and  ptosis 
is  not  rare.  Ectropion  has  been  observed  and  conjunctivitis 
is  a  rather  frequent  occurrence.  The  ocular  muscles  and  visual 
powers  fatigue  rapidly  so  that  pellagrins  are  rarely  able  to  per- 
form work  which  requires  close  inspection  for  any  length  of  time. 

Cataracts  are  not  infrequently  observed. 

Diplopia,  hemianopia,  and  photophobia,  especially  the 
latter,  are  very  common.  Marie^"*  states  that  he  has  seen 
patients  who  remained  for  years  with  eyes  closed  owing  to  the 
fear  of  light.  Bilateral  and  monolateral  mydriasis  is  seen. 
If  the  condition  is  confined  to  one  eye  the  right  is  the  one 
usually  affected.  The  pupillary  reflexes,  both  to  light  and 
accommodation,  are  frequently  sluggish. 

In  very  advanced  cases  are  seen  ulcers  of  the  cornea,  retinitis, 
choroiditis,  retinochroiditis  and  inflammation  of  the  optic  nerve. 

Sclerosis  of  the  retinal  vessels  and  dilatation  of  the  retinal 
veins  are  frequently  noted. 

All  these  symptoms,  as  would  be  expected,  appear  more 
exagerated  in  the  severe  cases  and  less  so  in  the  mild  ones. 

Marie^"^  gives  the  following  table  of  the  ocular  findings  of 
Ottolenghi,  Manfredi  and  Flarer: 

Number  examined 36 

Depth  of  eye  normal 12 

Changes  in  the  retina 15 

Atrophy  of  arteries 12 

Anomalies  in  fundus  of  left  eye i 

Anomalies  in  fundus  of  right  eye 6 

Atrophy  of  optic  nerve 3 

Increase  of  pigment 3 

Dilatation  of  the  veins i 


PELLAGRA  349 

The  other  special  senses  show  Uttle  or  no  derangements,  and 
certainly  nothing  which  may  be  regarded  as  pathognomonic. 

General  Symptoms. — Cachexia,  varying  from  slight  loss  of 
weight  to  great  emaciation,  is  observed.  The  cachexia  varies 
with  the  severity  of  the  disease  and  especially  with  the  severity 
of  the  diarrhea.  In  the  first  attack,  which  may  be  mild,  there 
may  be  little  or  no  loss  of  weight,  while  in  subsequent  attacks 
the  cachexia  often  advances  very  rapidly. 

The  temperature  in  uncomplicated  pellagra  is  usually  normal. 
Marie^*^  quotes  the  observations  of  Alpato-Novello  on  loo 
pellagrins.  He  states  that  22,274  observations  were  made, 
the  maximum  temperature  being  4i.5°C.  and  the  minimum 
35°C.;  2,059  were  above  normal  and  5,251  below  normal. 
Marie  further  states,  that  when  fever  does  occur  it  is  very  ir- 
regular, rarely  continuous  and  often  remittent,  almost  always 
with  an  evening  rise. 

The  pulse  rate  in  pellagra  is  usually  increased,  and  its  rate 
depends  upon  the  severity  of  the  disease.  During  the  acute 
attacks  it  may  run  as  high  as  100  or  more,  gradually  dropping 
to  normal  as  a  remission  occurs.  In  the  final  stages  it  often 
runs  as  high  as  130  or  more,  which  is  considered  a  grave  sign. 

In  spite  of  its  rapidity  the  pulse  is  usually  regular.  It  is, 
however,  soft  and  compressible  and  as  the  disease  progresses, 
decreases  in  volume. 

The  blood  pressure,  as  would  be  expected,  is  usually  low, 
except  in  pellagrins  with  arteriosclerosis.  Those  cases  which 
are  seen  in  the  terminal  stages  with  marked  cachexia  show  a 
very  low  blood  pressure;  one  case  in  particular  observed  by  one 
of  us  had  a  blood  pressure  of  only  85  mm. 

As  stated  in  the  chapter  on  pathology,  the  heart  frequently 
shows  hypertrophy,  atrophy,  hydropericardium  and  myocar- 
ditis. Endocarditis  with  incompetent  valves  is  rare,  although 
it  may  be  noted  as  a  complication. 

The  lungs  show  no  characteristic  symptoms,  though  as  stated 
above  pellagra  may  be  complicated  by  various  pathologic 
conditions  in  the  lungs,  which  will  display  typical  symptoms. 

Blood. — Most  investigators  have  found  that  there  is  usually 
a  deficiency  in  the  blood  stream  in  pellagra.     Not  only  is  the 


35°  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

total  volume  of  the  blood  diminished,  but  the  red  blood  cor- 
puscles and  hemoglobin  are  below  normal. 

The  anemia  is  usually  said  to  be  secondary  in  type,  that  is, 
the  decrease  in  the  hemoglobin  is  greater  than  the  decrease  in 
the  erythrocytes. 

Most  investigators  find  either  a  normal  or  slightly  increased 
leucocyte  count. 

Lavinder-*''  in  a  review  of  the  literature  of  the  hematology 
of  pellagra  gives  the  findings  of  the  following  investigators: 
Carletti  reviews  the  work  of  Lombroso,  Capezzuli,  Sepilli, 
Agostini  and  D'Ancona,  and  Randi,  and  noted  that  all  found 
similar  results,  viz.,  reduction  in  both  the  red  blood-cells  and 
the  hemoglobin  which  is  fairly  constant.  Sepilli  was  the  only 
one  who  reported  the  leucocyte  count,  which  he  found  to  be 
normal.  In  his  own  work  Carletti  found  a  constant  slight 
reduction  in  the  erythrocytes,  a  variable  number  of  whites 
(never  a  leucocytosis),  constant  reduction  in  the  hemoglobin 
(65-75  P^^  cent.)  with  a  low  color  index.  He  found  rather  a 
large  number  of  small  red  cells  and  the  varieties  of  leucocytes 
in  about  the  normal  proportions  with  a  possible  increase  in  the 
large  mononuclears ;  eosinophiles  were  rarely  found. 

Galesesco  and  Slatineano,  according  to  Lavinder,  found  in 
thirty-one  cases  a  constant  diminution  in  the  number  of  red 
cells  (three  to  four  million)  without  qualitative  changes; 
hemoglobin  (von  Fleischl)  from  70  to  90  per  cent. ;  slight  leu- 
cocytosis (nine  to  ten  thousand)  of  which  the  polynuclears  con- 
stituted 55  to  78  per  cent. ;  lymphocytes  17  to  33  per  cent. ;  large 
mononuclears  10  to  22  per  cent.;  eosinophiles  2  to  4  per  cent. 

These  investigators  conclude  that  there  is  a  large  mononuclear 
increase  from  which  no  deduction  can  be  drawn  as  to  etiology. 

In  a  study  of  thirty-four  cases,  Frateni  using  the  Thoma-Zeiss 
counting  apparatus  and  the  von  Fleischl  hemoglobinometer, 
found  a  rather  constant  reduction  in  the  number  of  red  cells 
(three  to  four  and  one-half  million)  and  in  the  hemoglobin 
(55  to  92  per  cent.)  leucocyte  counts  from  7,412  to  11,418. 
Differential  counts  showed  polynuclears  55  to  76  per  cent.,  large 
lymphocytes  2  to  5  per  cent.,  small  lymphocytes  18  to  39  per 
cent.,  eosinophiles  2  to  9  per  cent. 


PELLAGRA  351 

There  was  also  a  rather  constant  finding  of  macrocytes, 
microcytes  and  poikilocytes.  This  investigator  states  also  that 
he  found  nothing  resembling  a  protozoal  parasite. 

Lavinder  continues,  that  Manson  states  that  Sambon  and 
Terni  in  Italy,  and  Grigoresou  and  Galasesco  in  Roumania,  have 
noticed  a  relative  increase  in  the  large  mononuclear  leucocytes. 

Fiorini  and  Gavini  in  non-alienated  pellagrins  found  no 
leucocytosis,  but  a  typical  mononuclear  increase  and  a  decided 
eosinophilia. 

Masini,  Lavinder  states,  "in  a  study  of  the  eosinophile  cell 
in  the  blood  of  pellagrins  concludes  that,  contrary  to  what  is 
found  in  many  acute  infectious  diseases,  there  is  produced  in 
the  pellagrous  intoxication  a  conspicuous  and  decided  eosino- 
philia, which  occurs  in  cycles  corresponding  with  the  increase 
or  diminution  of  the  pellagrogenous  toxines;  that  is,  the  more 
toxemia  the  greater  the  eosinophilia.  He  suggests  that  this 
constant  eosinophilia  may  prove  at  times  a  valuable  aid  in  the 
early  differential  diagnosis." 

Peserico  found  the  following  percentages  of  the  varieties  of 
leucocytes:  polynuclears,  53.7  to  64.4;  lymphocytes,  26.1  to 
37.4;  large  mononuclears  and  transitionals,  1.2  to  7.7. 

These  results,  Lavinder  says,  in  many  ways  seem  decidedly 
discordant,  but  continues,  that  it  may  be  concluded  that  a 
usually  mild  secondary  anemia  is  very  frequent;  such  qualitative 
changes  in  the  red  cells  as  are  found  are  only  such  as  would  be 
expected.  The  only  factor  concerning  the  differential  leucocyte 
count  upon  which  there  is  an  agreement,  is  that  there  seems  to 
be  a  majority  opinion  of  a  definite  relative  large  mononuclear 
increase.  Lavinder's  own  work  consisted  of  twenty-four  ex- 
aminations. He  used  a  Thoma-Zeiss  counting  chamber  with 
Turck's  ruling;  in  counting  the  red  cells  the  four  corner  unit 
squares  (twenty-five  small  squares  each)  were  counted  in  two 
preparations,  and  if  the  results  were  discordant,  a  third  prepa- 
ration was  counted;  in  counting  the  leucocytes  the  whole 
ruled  space  was  counted  in  two  preparations,  and  again  if 
results  were  discordant,  a  third  preparation  was  counted.  A 
new  Dare  hemoglobinometer  which  gave  very  uniform  results 
in  normal  individuals  was  used  for  estimating  the  hemoglobin. 


352  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Lavinder  states  that  most  of  the  cases  were  of  an  advanced 
t3^e  showing  nervous  and  mental  symptoms,  and  nearly  all  in 
negro  women.  The  same  time  of  day  (morning)  was  chosen 
for  making  nearly  all  the  counts.  Many  had  been  taking 
arsenic  in  some  form  with  full  dosage  either  at  the  time  of  the 
examination  or  a  very  short  while  previously. 

Lavinder's  results  were  given  in  a  table  which  shows  that  the 
red  cell  count  ranged  from  2,826,640  to  5,520,000,  with  an 
average  of  4,474,000;  the  lowest  hemoglobin  reading  was  38 
per  cent,  (two  cases),  the  highest  95  per  cent,  and  the  average 
68  per  cent.,  while  the  leucocytes  varied  in  number  from  4,000 
to  17,000,  with  an  average  of  9,040.  The  average  color  index 
was  .77. 

Lavinder  does  not  tabulate  his  differential  counts  which 
were  not  made  in  all  cases,  but  states  that  there  was  an  increase 
in  the  large  mononuclears  and  no  eosinophilia  except  in  cases 
complicated  with  round  worms  or  hook-worms. 

Hillman^'^  in  thirty-two  examinations  of  twelve  pellagrins 
found  the  average  number  of  erythrocytes  to  be  4,758,000,  the 
average  hemoglobin  83  per  cent.,  with  the  following  percentages 
for  the  different  varieties: 

Polynuclears 59- 13  per  cent. 

Small  lymphocytes 29 .  36  per  cent. 

Large  lymphocytes 4  ■  63  per  cent. 

Large  mononuclears 2  .  59  per  cent. 

Transitionals 1.3°  P^r  cent. 

Eosinophiles 2 .  73  per  cent. 

Mast  cells 0.34  per  cent. 

Hillman  in  connection  with  Schule^^"  later  published  the 
results  of  further  investigations,  which  corroborated  the  find- 
ings described  above. 

Of  the  ninety-one  cases  seen  by  one  of  us  at  the  Arkansas 
State  Hospital  for  Nervous  Diseases  complete  blood  counts  were 
made  on  forty-eight.     The  table  on  page  353  shows  the  results. 

The  average  number  of  erythrocytes  was  3,800,000,  the 
average  hemoglobin  being  79  per  cent.  This  gives  a  rather 
high  average  color  index. 

The  average  number  of  leucocytes  was  8,500  with  an  average 


PELLAGRA 


353 


SS 


6,S78 

6,222 


7.090 
S.S2I 
7. 119 
6,968 

6,432 
6,977 
5.906 
6.797 
4.893 


7.292 
7.301 
7.319 


7.148 
S.6S3 
S.967 
7,164 
6,418 

6.701 
6.992 
6.691 
6,7SS 
6,380 

6.720 
7.036 
6.334 


7,323 
S,004 
6,390 


3.220 
3,460, 
3.950, 
4.390, 
2,000, 

4.180, 
3,920 
4,020 
4,640 
3,360, 

4.870, 
3.320, 
2,880, 
5,590, 
4.500, 

4.240, 
3,710 
S,OSO 
3.650 
4.400, 

4.430, 
2.880, 
3,680, 
3.SIO, 
3,410 


3.880, 
4.400, 

4.130, 
4.040, 
3.960 
4.350 
3.670, 

4.740, 
.3.180, 
4.830, 
4.370, 
4.760 

3.SSO, 


4.230, 
3.940, 

4.670, 
3.660, 
3.580, 


.000 

64 

,000 

90 

,000 

85 

,000 

82 

,000 

88 

,000 

68 

,000 

70 

6,400 
6,200 
6,400 
S,S6o 
4.700 

9.500 
18,400 

lO.SOO 

15.400 
4.400 

8,000 
5.500 
11,600 


7,700 
12,200 
6,200 
6,200 


7,600 
6,600 
9.600 
11,000 
9,200 


6,400 
4,600 
7.400 
10,200 

8,200 
7,600 
6,200 


18,200 

79 

5,600 

5t 

5,480 

70 

9,000 

79 

9,000 

67 

7,000 

76 

10,800 
9,600 
12,200 


354  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

of  72  per  cent,  polymorphonuclears  and  24.5  per  cent.  lympho- 
cytes. Eosinophiles  were  found  in  only  twenty  cases,  the  high- 
est percentage  being  2  and  that  in  only  one  case. 

Numerous  investigators  have  made  blood  cultures  from  pel- 
lagrins, using  every  conceivable  medium  and  under  both  aerobic 
and  anaerobic  conditions,  but  with  uniformly  negative  results. 

While  no  definite  data  are  to  be  found  concerning  the  coagu- 
lability of  the  blood  of  pellagrins,  in  a  rather  extensive  experience 
with  such  blood  in  making  various  tests  and  examinations  we 
have  never  noticed  any  abnormalities  in  the  time  of  coagulation. 

Wassermann  Test. — Several  investigators  have  applied  the 
Wassermann  complement  fixation  test  to  the  blood  of  pellagrins. 

Bass,'''  using  an  alcoholic  lecithin  antigen,  reported  six  posi- 
tive reactions  in  pellagra.  Later'*"  he  reported  on  ten  more 
cases.  Four  of  the  sixteen  cases  were  ruled  out  on  account  of 
malaria,  syphilis  or  autopsy  blood.  Of  the  remaining  cases 
eight  were  positive,  seven  of  them  being  mild  or  chronic  cases 
and  one  a  severe  case,  while  four  were  negative  cases. 

Fox,-**  using  the  Noguchi  modification  of  the  Wassermann, 
secured  eight  weakly  or  moderately  positive  and  twenty-two 
negative  reactions  with  thirty  cases.  Carletti,  using  the  origi- 
nal Wassermann  technic,  tested  the  sera  of  twenty  pellagrins, 
securing  all  negative  results.  With  Bass'  lecithin  antigen  he 
secured  one  positive,  the  others  all  being  negative.  One  of  us 
using  the  technic  described  by  him"^  performed  the  Wasser- 
mann reaction  on  thirty-five  pellagrins  with  uniformly  negative 
results. 

In  attempting  to  develop  a  complement  fixation  test  for 
pellagra  one  of  us  prepared  an  antigen  by  macerating  portions 
of  the  brain,  spinal  cord,  skin  (the  area  affected  with  the  der- 
matitis) and  intestinal  mucosa  washed  thoroughly,  and  ex- 
tracting with  alcohol. 

The  technic  employed  was  that  described  by  one  of  us,'" 
while  the  amount  of  antigen  used  was  an  amount  a  little  less 
than  would  slightly  inhibit  hemolysis  with  the  pooled  sera  of 
several  known  normal  individuals. 

The  sera  of  ten  pellagrins  with  active  lesions  were  examined 
with  absolutely  negative  results. 


PELLAGRA  355 

Nitzesco^'*  claimed  to  have  been  able  to  diagnose  pellagra 
with  a  dialization  test,  using  Abderhalden's  ninhydrin  technic 
with  a  maize  albumin  or  zein.  The  reaction  was  particularly 
pronounced  with  eight  cases  with  predominating  gastro-in- 
testinal  symptoms,  and  negative  with  fifty-six  non-pellagrins 
and  two  pellagrins  who  had  been  in  the  hospital  for  over  two 
years  and  had  eaten  no  maize  during  this  time  and  had  had  no 
symptoms  except  slight  mental  confusion  at  times.  Another 
case  with  merely  nervous  manifestations  was  shown  by  the 
serologic  test  to  be  suffering  from  an  otherwise  latent  pellagra 
and  later  developed  other  characteristic  symptoms. 

Nitzesco's  work  has  not  been  confirmed  and  in  the  light  of 
the  present  evidence  against  the  corn  theory  of  the  etiology  of 
pellagra  must  be  taken  with  the  greatest  reserve. 

Urine. — The  urine  of  pellagrins  shows  nothing  characteristic, 
although  certain  abnormalities  very  frequently  occur.  Marie'"^ 
states  that  in  loo  pellagra  patients  the  24-hour  quantity 
showed  an  average  of  900  c.c.  with  a  minimum  of  500  c.c.  and 
a  maximum  of  1,900  c.c.  He  also  found  marked  variation 
in  the  reaction  as  follows:  76  times  slightly  acid;  14  times 
neutral;  and  10  times  alkaline.  The  specific  gravity  ranged 
from  1,005  to  1,025.  Albumin  was  found  but  twice  in  no 
urines. 

Most  investigators  find  indican  a  very  frequent  constituent 
of  pellagrous  urine.  Thus  Watson'"^  found  indican  present  175 
times  in  180  urines.  Meyers  and  Fine^^^  found  indican  in 
large  quantities  in  all  of  the  14  cases,  while  the  Illinois  Pellagra 
Commission^"^  found  a  very  marked  reaction  in  all  cases. 

Of  the  ninety-one  cases  seen  by  one  of  us  at  the  Arkansas 
State  Hospital  for  Nervous  Diseases,  urinalyses  were  made 
for  thirty-nine. 

The  table  on  page  356  shows  the  results. 

It  will  be  seen  that  the  specific  gravity  varied  from  1,003 
to  1,030  with  an  average  of  i,or8.  The  reaction  was  acid  in 
all  but  two  cases,  it  being  neutral  in  them.  Alkaline  urine  was 
not  observed.  Indican  was  found  eleven  times  usually  only 
in  traces,  although  some  cases  showed  a  fairly  strong  reaction. 

Albumin  was  found  five  times,  hyaline  and  granular  casts 


3S6 


ENDEMIC   DISEASES    OF    THE    SOUTHERN    STATES 


twice — once  in  a  urine  containing  albumin  and  once  in  one  free 
from  that  protein.     Sugar  was  not  found  in  any  of  the  cases. 


Case  No. 

Sp.  gr. 

Reaction 

Indican 

Albumin 

Sugar 

Casts 

I 

1,016 

Acid 

Trace 

Negative 

Negative 

Negative 

2 

1,016 

Acid 

Trace 

Negative 

Negative 

Negative 

3 

1,026 

Acid 

Negative 

Positive 

Negative 

Negative 

4 

1,003 

Acid 

Negative 

Negative 

Negative 

Negative 

5 

1,022 

Acid 

Trace 

Positive 

Negative 

Negative 

6 

1,022 

Acid 

Positive 

Negative 

Negative 

Negative 

7 

1,024 

Acid 

Negative 

Positive 

Negative 

Negative 

8 

1,014 

Acid 

Negative 

Negative 

Negative 

Negative 

9 

1,028 

Acid 

Negative 

Negative 

Negative 

Negative 

lO 

1,020 

Acid 

Trace 

Negative 

Negative 

Negative 

II 

1,022 

Acid 

Negative 

Negative 

Negative 

Negative 

12 

1,018 

Acid 

Negative 

Positive    ■ 

Negative 

Negative 

13 

1,024 

Acid 

Negative 

Negative 

Negative 

HandG 

14 

1,010 

Neutral 

Negative 

Negative 

Negative 

Negative 

IS 

1,010 

Acid 

Negative 

Negative 

Negative 

Negative 

i6 

1,030 

Acid 

Positive 

Negative 

Negative 

HandG 

17 

1,020 

Acid 

Negative 

Negative 

Negative 

Negative 

18 

1,016 

Acid 

Negative 

Negative 

Negative 

Negative 

19 

1,020 

Acid 

Negative 

Negative 

Negative 

Negative 

20 

1,026 

Neutral 

Negative 

Negative 

Negative 

Negative 

21 

1,012 

Acid 

Negative 

Negative 

Negative 

Negative 

22 

1,026 

Acid 

Negative 

Negative 

Negative 

Negative 

-3 

1,020 

Acid 

Negative 

Negative 

Negative 

Negative 

24 

1,022 

Acid 

Trace 

Negative 

Negative 

Negative 

25 

1,022 

Acid 

Negative 

Negative 

Negative 

Negative 

26 

1,018 

Acid 

Negative 

Negative 

Negative 

Negative 

27 

i,oiS 

Acid 

Negative 

Negative 

Negative 

Negative 

28 

1,020 

Acid 

Positive 

Negative 

Negative 

Negative 

29 

1,004 

Acid 

Negative 

Negative 

Negative 

Negative 

30 

1,020 

Acid 

Positive 

Negative 

Negative 

Negative 

31 

1,020 

Acid 

Negative 

Positive 

Negative 

Negative 

32 

1,028 

Acid 

Negative 

Negative 

Negative 

Negative 

33 

1,026 

Acid 

Trace 

Negative 

Negative 

Negative 

34 

1,016 

Acid 

Negative 

Negative 

Negative 

Negative 

35 

1,010 

Acid 

Positive 

Negative 

Negative 

Negative 

36 

1,010 

Acid 

Negative 

Negative 

Negative 

Negative 

37 

1,028 

Acid 

Negative 

Negative 

Negative 

Negative 

38 

1,008 

Acid 

Negative 

Negative 

Negative 

Negative 

39 

1,018 

Acid 

Negative 

Negative 

Negative 

Negative 

Gastric  Contents. — The  gastric   contents   following  a   test 
meal  have  been  analyzed  by  numerous  investigators.     Lom- 


PELLAGRA 


357 


broso,  Filippi  and  Roncoroni,  according  to  Marie, ^"^  made  four 
tests  each  of  the  gastric  contents  of  two  pellagrins.  The  test 
meal  consisted  of  a  porringer  of  soup,  85  grams  of  meat,  200 
grams  of  bread  and  100  grams  of  wine.  The  length  of  time 
the  meal  was  allowed  to  remain  in  the  stomach  is  not  stated. 
The  following  table  shows  the  results  in  detail: 


Analyses 

Case  I 

Case  2 

Reaction  of  gastric  juice. 

Once  neutral;  three  times 
slightly  acid. 

Acid. 

Hydrochloric  acid  (Guns- 

Always  negative. 

Always  negative. 

berg  reaction). 

Lactic    acid    (Uffelmann 

Present  three  times  out  of 

Always  appreciable. 

reaction). 

four. 

Percentage  of  acidity. .  .  . 

Average  60  per  cent. 

Average  50  per  cent. 

Peptone     (Biuret     reac- 

Present. 

Present. 

tion). 

Digestion  of  starclies. .  .  . 

Twice     complete;     once 

Three     times     complete; 

arrested   in   the   second 

once     arrested     in     the 

stage. 

first  stage. 

The  following  table  is  part  of  one  quoted  by   Roberts'"'' 
from  the  work  of  J.  Clarence  Johnson: 


No. 

Test  meal 

Case  No. 

Test  meal 

I 

HCl  -  R  - 

II 

HCl  -  R  -i- 

2 

HCl  -  R  -f 

12 

•     HCl  -  R  -1- 

3 

HCl  -  R  - 

13 

HCl  -  R  - 

4    • 

HCl  -  R  + 

14 

G  -1-  F  30  T  38 

S 

HCl  -  R  + 

IS 

G  -f  F  24  T  42 

6 

G  -1-  F  36  T  66 

16 

G  -  F  18  -  T  38 

7 

G  -f  F  38  T  74 

17 

HCl  -  R  -H 

8 

HCl  -  R  - 

18 

HCl  -  R  - 

9 

HCl  -  R  -h 

19 

HCl  -  R  - 

0 

G  -h  F32T50 

20 

HCl  -  R  - 

HCl  =  hydrochloric  acid;  R  =  renin;  F  =  free  (presum- 
ably free  HCl,  L.  T.);  T  =  total  acid;  G  =  Gunzburg's  test. 

It  is  not  stated  what  test  meal  was  used  by  this  investigator 
nor  the  length  of  time  it  remained  in  the  stomach. 

Nisbet-^^  made  fifteen  analyses  on  ten  cases  but  he  also  failed 
to  give  data  concerning  the  test  meal  and  the  period  of  diges- 
tion.    The  following  table  is  compiled  from  his  findings: 


3S8 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


Case  No. 

T.  A. 

Free  HCl 

Ferments 

Mucus 

30 
28 
80 
40 
28 
33 
24 
18 
56 
76 
42 

22 
40 

5° 
0 

0 

4 

35 

10 

4 
8 
0 
4 
24 
39 
20 
8 

19 

20 
0 

XXX 

Diminution 

Normal 

XXX 

XXX 

Diminution 

XXX 

Normal 

Normal 

XXX 

XXX 

XXX 

Normal 

XXX 

XXX 

3.  Second  analysis 

3.  Third  analysis 

Normal 
Normal 

4.   Second  analysis 

Excess 

6 

7 

7.  Second  analysis 

Excess 
Normal 
Normal 

8 

9 

Normal 
Excess 

It  will  be  seen  from  the  above  that  the  most  constant  find- 
ings in  the  gastric  contents  in  pellagrins  is  a  diminution  in  the 
total  acidity  and  the  free  hydrochloric  acid.  This  is  no  more 
than  would  be  expected  from  the  pathologic  findings  and 
cannot  be  considered  at  all  pathognomonic. 

Feces. — The  feces  of  pellagrins  vary  greatly  in  consistency 
and  volume.  The  consistency  varies  with  the  degree  of 
diarrhea  or  constipation,  from  watery  stools  to  hard  stools,  and 
according  to  Myers  and  Fine^^^  the  daily  elimination  varies 
from  60  to  700  grams  of  moist  feces,  yielding  20-40  grams  of 
dry  excrement,  the  moisture  varying  between  75  and  95  per 
cent.  There  is  usually  an  increase  in  the  undigested  food 
particles,  especially  muscle  libers,  starch  granules  and  fats. 

The  fact  that  the  feces  of  pellagrins  very  frequently  contain 
amebas,  which  are  considered  by  some  of  etiologic  significance, 
has  been  mentioned  in  the  chapter  on  etiology.  Other  animal 
intestinal  parasites  such  as  uncinaria,  strongyloides,  trichiuris, 
ascaris,  etc.,  have  been  found  but  are  without  doubt  merely 
incidental  and  bear  no  relation  to  the  etiology  of  the  disease. 

The  fecal  flora  of  pellagrins  has  been  the  subject  of  study  by 
numerous  investigators  who  have  hoped  to  discover  the 
etiological  factor. 

McNeaP^"  found  that  there  were    present    unusual    quan- 


PELLAGRA  359 

titles  of  certain  types  of  bacteria  which  are  normally  found 
in  the  intestinal  tract,  such  as  B.  bifidus,  B.  welchii  and  micro- 
cocci, as  well  as  a  large  number  of  organisms  not  found  in 
normal  feces.  McNeal  states  that  none  of  these  changes 
appear  constant.  During  the  acute  attack  when  diarrhea  is 
present  the  Gram-positive  cocci  are  nearly  always  abnormally 
numerous  and  Gram-negative  bacilli  less  numerous  than 
normal.  McNeal  continues  that  these  changes  are  also  ob- 
served in  the  subacute  cases  and  might  persist  to  a  slight 
degree  after  recovery  from  the  skin  lesions.  They  are  nearly 
constant,  but  are  such  as  might  be  expected  as  a  natural  result 
of  digestive  derangement.  This  investigator  further  states 
that  there  was  no  indication  that  a  substitution  of  normal 
bacteria  by  abnormal  ones  occurred. 

Spinal  Fluid. — The  spinal  fluid  of  pellagrins  has  been  the 
subject  of  investigation  by  several  workers. 

Marie^"^  states  that  the  spinal  fluid  is  found  to  be  negative. 

Boveri,^'*-  on  the  other  hand,  found  an  increase  in  albumin 
and  a  slight  pleocytosis  in  the  spinal  fluid  of  pellagrins. 

This  is  somewhat  in  accord  with  the  findings  of  Hindmann-^^ 
who  in  191 2  reported  the  results  of  the  examination  of  the  spinal 
fluids  of  over  ninety  insane  pellagrins.  He  found  an  average 
cell  count  of  16.69  cells  per  cubic  millimeter,  with  64  as  the 
maximum  where  no  complication  existed.  Seventy-four,  or 
over  87  per  cent.,  of  eighty-five  specimens  showed  increase 
in  globulin  by  Noguchi's  butyric  acid  test. 

Later  Hindmann'^'*^  revised  his  conclusions  to  a  certain  ex- 
tent, stating  that  some  of  the  cases  in  which  a  pleocytosis  and 
increase  in  globulin  exist  show  positive  evidence  of  syphilis, 
although  "many  cases  have  shown  a  decided  increase  in  globulin 
and  slight  increase  in  cells,  and  invariably  gave  negative 
Wassermann  reactions." 

The  Illinois  Pellagra  Commission^**  found  the  spinal  fluid 
of  pellagrins  without  increase  in  the  cellular  elements  and 
globulin  and  sterile. 

Lorenz,"^  who  has  made  the  most  detailed  study  of  the 
spinal  fluid  in  pellagrins  yet  reported,  after  examining  153  fluids 
from  106  cases  of  pellagra  reached  the  following  conclusions: 


360  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

1.  A  lymphocytosis  of  the  cerebrospinal  fluid  does  not  occur 
in  uncomplicated  pellagra. 

2.  Globulin  excess  is  only  occasionally  observed. 

3.  Lange's  colloidal  gold  chloride  test  is  uniformly  negative 
in  pellagra. 

4.  The  Wassermann  is  negative  with  a  few  exceptions.  In 
this  investigation  the  exceptions  were  moribund  cases  which 
gave  weakly  positive  reactions  with  blood  serum. 

5.  The  spinal-fluid  findings  would  seem  inconsistent  with  a 
conception  that  pellagra  is  an  infectious  disease  of  the  central 
nervous  system. 

In  a  limited  number  of  cases  the  findings  of  one  of  us  have 
been  in  accord  with  those  of  Lorenz.  In  six  cases  upon  whom 
lumbar  puncture  was  performed  at  the  Arkansas  State  Hospital 
for  Nervous  Diseases  the  spinal  fluid  showed  no  pleocytosis  nor 
increase  in  globulin  and  the  Wassermann  was  negative. 

Types  of  Pellagra. — While  pellagra  is  without  doubt  a 
morbid  entity  showing  many  characteristic  symptoms  and 
lesions,  it  very  frequently  assumes  different  forms,  certain 
symptoms  predominating,  so  that  various  types  of  the  disease 
have  been  described.  One  of  the  most  interesting  conditions 
seen  in  pellagra  is  that  described  as  typhoid,  the  so-called 
typhus  pellagrosus.  This  is  a  most  unfortunate  term,  for, 
while  pellagra  is  occasionally  complicated  by  typhoid,  there 
is  nothing  in  the  condition  usually  termed  typhoid  pellagra  to 
warrant  this  name. 

This  condition  is,  however,  characterized  by  great  prostra- 
tion. It  may  begin  either  as  an  acute  outbreak  developing 
suddenly,  or  as  an  incidence  to  the  chronic  course  of  pellagra, 
or  finally  it  may  mark  the  fatal  ending  of  the  disease. 

Fever  is  usually  present  to  a  more  or  less  marked  degree,  the 
temperature  ranging  from  99°  to  io5°F.  The  fever  is  con- 
tinuous, without  morning  or  evening  variation.  The  pulse  is 
rapid,  rarely  falling  below  no,  and  may  run  as  high  as  130-140. 
This  height  is  out  of  proportion  to  the  temperature,  which  is 
the  reverse  of  the  condition  in  typhoid  fever.  The  pulse  is 
small  and  often  irregular. 

The  gastro-intestinal  symptoms  are  accentuated,   the  sto- 


PELLAGRA  361 

matitis  and  gastroenteritis  being  present  to  a  marked  degree. 
Diarrhea  of  a  persistent  type  is  seen,  the  stools  being  as  a  rule 
of  watery  consistency. 

The  mental  symptoms  are  nearly  always  aggravated.  There 
may  be  delirium  or  there  may  be  stupor. 

The  nervous  phenomena  are  most  marked.  Tremors  of  the 
hands,  tetanic  contractions,  convulsions,  and  opisthotonos  are 
seen.     There  may  be  incontinence  of  the  urine  and  feces. 

The  course  of  the  attack  is  usually  short — from  one  to  two 
weeks — and  nearly  always  ends  fatally,  often  with  a  terminal 
bronchitis. 

Recovery  from  the  attack  may,  however,  occur,  but  there  is 
always  a  recurrence. 

Pellagra  sine  pellagra,  mention  of  which  has  been  made  above, 
is  a  condition  in  which,  as  the  term  implies,  other  symptoms  of 
pellagra  than  the  skin  lesions  alone  are  present.  Whether  or  not 
pellagra  can  exist  without  the  skin  manifestations  being  present 
at  some  time  during  the  course  of  the  disease  is  a  moot  point. 
Lombroso  as  well  as  Strambio  recognized  this  condition,  the 
former  considering  that  it  appeared  only  in  an  hereditary  form. 

It  seems  to  us  that  if  pellagra  sine  pellagra  does  exist  it  is 
an  extremely  rare  condition,  and  that  in  any  given  case  the 
skin  eruption  has  either  already  occurred  without  recognition 
and  has  faded  or  it  will  occur.  Most  cases  exhibiting  other 
symptoms  of  pellagra  will,  upon  a  careful  anamnesis,  give  the 
history  of  some  sort  of  skin  manifestation  attributable  to 
pellagra,  perhaps  a  severe  sunburn  or  a  roughening  of  the 
skin  of  the  elbow. 

Other  types  of  pellagra  have  been  described,  such  as  cerebral, 
spinal,  tabetic,  spastic,  gastric,  atrophic,  cutaneous,  enteric, 
etc.,  depending  upon  the  symptoms  which  are  predominant. 

Duration. — The  duration  of  pellagra  is  most  variable.  The 
severe  acute  attacks  that  sometimes  occur  may  end  fatally 
in  from  one  to  two  weeks  or  the  disease,  which  is,  as  has  been 
reiterated,  a  chronic  one,  may  last  with  recurrences  and  periods 
of  remission  for  five,  ten,  fifteen  years  or  longer.  Sambon^-- 
states  he  has  seen  pellagrins  who  declared  they  had  had  the 
disease  for  twenty,  thirty  or  more  years.     He  tells  of  cases 


362  ENDEMIC   DISEASES    OF   THE    SOUTHERN   STATES 

eighty  years  of  age  who  claimed  to  have  been  pellagrous  since 
childhood. 

Albright'*^  gives  the  following  concerning  the  duration  of 
the  disease: 

Number 
of  cases 

To    I  year 160 

To    2  years 67 

To    3  years 34 

To    4  years 13 

To    s  years 6 

To    6  years 2 

To    7  years 3 

To    8  years 7 

To  10  years i 

To  II  years 3 

To  15  years i 

Unknown 19 

Of  course  the  duration  of  pellagra  will  depend  upon  the 
severity  of  the  symptoms. 

As  stated,  the  acute  attacks  sometimes  terminate  in  death  in 
as  short  a  time  as  one  week,  or  they  may  last  as  long  as  three 
months,  a  remission  following  and  the  disease  recurring  again 
the  following  year. 

The  number  of  recurrences  will,  as  can  readily  be  seen,  de- 
pend upon  their  severity,  the  first,  second,  third  or  later  attack 
proving  fatal,  or  the  attacks  may  be  mild,  extend  over  a  period 
of  years,  and  the  patient  succumb  to  some  intercurrent  disease. 

Complications. — As  may  readily  be  imagined,  a  disease  so 
chronic  in  its  nature  as  pellagra  will  very  frequently  be  com- 
plicated by  other  diseases.  This  is  certainly  true,  and  there  is 
scarcely  an  ill  to  which  human  flesh  is  heir  which  may  not  be 
found  in  conjunction  with  pellagra. 

As  has  been  mentioned  above,  pellagra  has  been  found  very 
frequently  complicated  by  ankylostomiasis  and  amebse  by 
various  investigators,  and  according  to  Sambon^"*^  the  infection 
with  hook-worm  disease  accounts  in  a  large  measure  for  the 
anemia  found  in  pellagrins.  Other  intestinal  parasites  found 
more  or  less  frequently  complicating  pellagra  are  Ascaris 
lumbricoides,  Trichiuris  irickiura,  oxyuris  vermicularis ,  Cerco- 
monas  hominis  and  Hymenolepis  nana. 


PELLAGRA  363 

Sandwith^^^  says  that  in  Italy  pellagra  is  often  complicated 
by  alcoholism,  syphilis  and  malaria,  but  that  in  Egypt  alcohol 
plays  a  small  part.  He  finds  it,  however,  frequently  associated 
with  ankylostomiasis,  bilharziosis,  and  favus  of  the  scalp. 

Alcoholism  is  certainly  a  frequent  complication  in  this 
country,  and  Marie'"^  considers  that  it  may  be  difficult  to 
determine  which  of  the  symptoms  are  due  to  pellagra  and  which 
to  alcohol. 

Tuberculosis  is  a  rather  frequent  complication  of  pellagra 
and  may  be  found  affecting  either  the  lungs  or  other  portions 
of  the  body,  especially  the  intestines. 

Sambon'^^  states  that  in  Italy  pellagra  is  frequently  found 
in  conjunction  with  scurvy. 

That  pellagrins  are  also  not  infrequently  syphilitics  is  un- 
doubted. This  is  borne  out  by  the  statements  of  many  ob- 
servers— Marie, '"^  Sandwith^"  and  others. 

It  has  been  pointed  out  above  that  pellagra  not  infrequently 
develops  in  the  insane,  even  in  individuals  who  have  been 
patients  in  insane  hospitals  for  many  years.  It  may  therefore 
be  said  to  complicate  any  of  the  psychoses.     (See  page  359.) 

Many  pellagrous  women  are  sufferers  from  gynecologic  com- 
plications, dysmenorrhea,  amenorrhea,  menorrhagia,  leucorrhea, 
etc.,  and  in  male  pellagrins  a  urethritis  is  not  uncommon. 

According  to  Lavinder^"*^  certain  investigators,  especially  in 
Italy,  consider  that  chronic  alcoholism  may  produce  in  its 
victims  a  condition  much  resembling  pellagra,  even  including 
skin  manifestations  similar  to  those  of  this  disease.  This  con- 
dition comes  under  the  classification  of  pseudopellagra  according 
to  the  Italians,  but  Lavinder  considers  it  a  true  pellagra. 

Roberts'""  gives  the  following  table  showing  the  complica- 
tions seen  by  him: 

Number  of  patients 31 

Pulmonary  tuberculosis 10 

Syphilis S 

Valvular  heart  disease 10 

Arteriosclerosis 6 

Chronic  nephritis i 

Enlarged  thyroid 2 

Bronchitis,  chronic i 

Drug  habit i 


364  ENDEMIC   DISEASES    OF   THE    SOUTHERN    STATES 

Albright''"  in  an  analysis  of  298  cases  gives  the  following 
table  of  complications: 

Hook-worm. 10 

Tuberculosis 18 

Mental 4 

Age 8 

Invalid 4 

None 168 

Syphilis 6 

Typhoid  disease 25 

Indigestion 4 

Epilepsy 3 

Alcoholism 2 

Other  diseases 46 

Pregnancy  and  Pellagra. — Mention  of  a  possible  relation  of 
pregnancy  in  pellagra  as  a  predisposing  cause  of  the  malady 
has  been  made  above. 

Saunders-^^  states  that  17  per  cent,  of  pregnant  pellagrous 
women  are  liable  to  abort,  to  give  birth  to  still-born  infants, 
and  at  delivery  to  post-partum  hemorrhage.  This  author 
further  states  that  gestation  and  lactation,  especially  when 
frequent,  predispose  to  pellagra,  and  that  parturition  is  often 
an  exciting  cause  for  the  outbreak  of  the  dermatitis. 

Recurrences. — In  what  has  gone  before  we  have  made  use 
of  the  term  recurrences  in  describing  the  repeated  outbreaks 
of  the  pellagrous  symptoms,  but  it  is  not  an  absolutely  proven 
fact  that  these  repeated  outbreaks  are  recurrences  and  it  is 
recognized  that  they  may  be  reinfections. 

It  seems  to  us,  however,  that  the  well-known  fact  of  certain 
individuals  suffering  from  repeated  attacks  of  pellagrous 
symptoms  year  after  year  and  the  comparative  rarity  of  those 
suffering  from  one  attack  and  remaining  well  is  almost  proof 
of  the  theory  of  recurrent  attacks.  However,  we  admit  that 
this  question  cannot  be  settled  with  finality  until  the  etiologic 
factor  is  known,  or  at  least  until  some  means  of  determining 
when  a  pellagrin  is  cured  other  than  the  absence  of  pellagrous 
symptoms  is  developed. 

Pseudopellagra. — This  term  was  first  applied  by  Roussel 
to  a  certain  symptom-complex  which,  while  resembling 
pellagra  to  a  certain  extent,   was   to   his   mind   not   related 


PELLAGRA  365 

to  that  disease.  Pseudopellagra  has  received  scant  atten- 
tion in  this  country,  and  such  attention  as  it  has  received 
is  more  or  less  in  the  nature  of  ridicule  of  the  idea.  How  can 
there  be  a  pseudopellagra  when  the  essential  nature  of  the  disease 
is  unknown?  Of  course  most  of  those  who  employ  this  term 
believe  in  the  corn  theory  of  the  etiology  of  pellagra  and  there- 
fore make  the  disease  conform  to  the  supposed  etiology. 
That  is,  if  a  symptom-complex  resembling  pellagra  develops 
in  an  individual  who  does  not  use,  nor  has  not  used,  maize, 
it  is  termed  pseudopellagra. 

Of  course  inasmuch  as  the  etiologic  factor  of  pellagra  is 
unknown,  we  admit  it  is  possible  that  there  are  other  conditions 
which  resemble  this  malady  but  are  distinct  from  it.  Thus, 
if  the  disease  is  due  to  a  parasite,  there  may  be  similar  parasites 
which  cause  similar  clinical  pictures  but  when  the  cause  is 
known  will  be  readily  differentiated.  A  similar  condition  is 
found  in  typhoid  and  paratyphoid  infections,  which  show  great 
similarity — and  which  are  caused  by  very  similar  bacteria  but 
which  may  be  differentiated  by  cultural  procedures. 

The  following  case  observed  by  one  of  us  at  the  Arkansas 
State  Hospital  for  Nervous  Diseases  is  illustrative: 

Case  No.  I. — J.  S.  U.,  white  man,  aged  twenty-two  years, 
single,  college  student. 

Family  History. — His  father  is  said  to  have  shown  signs  of 
mental  derangement  for  the  past  ten  years,  being  of  a  sad 
disposition  and  continually  wanting  to  "trade."  He  was 
brought  to  the  Arkansas  State  Hospital  for  Nervous  Diseases 
in  October,  191 1,  where  he  remained  for  six  months  when 
he  was  discharged.  Eight  months  later  he  again  developed 
acute  mental  symptoms  and  when  upon  his  way  to  the  above 
hospital  escaped  and  has  not  been  heard  of  since.  The  patient's 
grandmother  also  was  said  to  have  been  insane. 

Previous  History. — No  history  of  previous  illness  was  ob- 
tained, the  patient  stating  that  he  had  been  healthy  all  his  life. 

Present  Illness. — The  patient  states  that  an  eruption  on  the 
backs  of  the  hands  has  appeared  each  spring  for  the  past  six 
years,  seeming  to  grow  a  little  worse  each  time.  Attacks 
were  accompanied  by  diarrhea  and  sore  mouth.     He  says  that 


366  NDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

the  duration  of  the  present  attack  has  been  longer  than  any 
other. 

Examination  July  25,  191 3. — The  patient  is  not  emaciated, 
the  muscles  being  well  formed  and  firm.  The  general  nutri- 
tion is  good.  The  chest  is  full  and  well  formed,  expansion  is 
thoracic-abdominal  in  character.  The  lungs  are  negative  to 
auscultation,  palpation  and  percussion.  The  heart  is  normally 
situated  and  there  are  no  murmurs  audible.  His  pulse  is  of  good 
volume,  medium  tension  and  regular.  The  rate  is  96  per 
minute,  reclining  posture. 

The  systolic  blood  pressure  is  no  taken  in  the  right  arm, 
patient  in  reclining  posture.  The  abdomen  is  negative  and 
the  spleen  and  liver  are  not  palpable.  The  tongue  is  moist 
and  only  slightly  coated  and  the  teeth  are  in  fair  condition. 
The  skin  is  dark  over  the  entire  body  and  is  free  from  eruption, 
except  beginning  at  the  elbow  on  each  arm  and  extending  down 
over  the  backs  of  the  hands  and  forearms  there  is  a  dry  con- 
dition and  the  superficial  layer  of  the  epidermis  is  exfoliating 
in  places. 

Blood  Examination. — Erythrocytes  2,870,000,  hemoglobin 
58  per  cent.,  leucocytes  17,000. 

A  diagnosis  of  pellagra  was  made,  but  on  account  of  lack 
of  sufficient  evidence  no  diagnosis  of  a  psychosis  was  made  and 
the  patient  was  paroled  August  2,  1913.  For  a  few  weeks  his 
condition  was  favorable,  but  he  soon  developed  symptoms  of 
restlessness  and  insomnia  and  attempted  suicide,  and  was 
therefore  readmitted  to  the  hospital  November  27,  1913. 
At  this  time  his  cutaneous  manifestations  were  most  marked, 
and  he  soon  developed  diarrhea  and  fever. 

A  Widal  test  was  negative  as  was  a  Wassermann  upon  his 
blood.  The  spinal  fluid  showed  a  negative  Wassermann,  three 
lymphocytes  per  cubic  millimeter  and  no  increase  in  globulin. 
He  was  placed  upon  sodium  cacodylate  i  grain  three  times  a 
day,  but  steadily  grew  worse. 

On  December  12,  1913,  he  received  0.3  gram  neosalvarsan 
intravenously.  On  December  15  this  treatment  was  repeated. 
December  16  his  temperature  became  subnormal  and  he 
gradually  passed  into  coma,  dying  Dec.  17,  1913. 


PELLAGRA  367 

Case  No.  II. — H.  M.,  white  man,  aged  thirty-nine  years,  no 
occupation. 

Family  History. — Four  members  of  the  immediate  family 
have  been  addicted  to  the  use  of  morphine.  No  cases  of 
pellagra  have  occurred  in  the  family. 

Previous  Illness. — He  has  had  very  little  sickness,  none  of  a 
serious  nature.  About  twenty  years  ago  he  began  the  use  of  mor- 
phine and  is  now  taking  25  to  30  grains  daily.  He  has  abused 
alcohol  for  a  number  of  years  and  has  been  drinking  regularly 
for  the  past  three  months.  He  smokes  about  a  sack  of  tobacco 
daily  as  cigarettes.  The  regular  weight  is  about  200,  now 
weighs  160. 

Present  Illness. — About  four  weeks  ago  the  legs  began  to 
ache,  then  got  weak  and  numb  and  began  to  tingle.  They 
pain  considerably  now.  He  feels  very  weak  from  the  knees 
down  but  is  strong  elsewhere.  The  eruption  began  on  the 
backs  of  the  hands  three  weeks  ago.  Four  or  five  weeks  ago 
the  mouth  became  sore  and  is  still  inflamed.  He  has  no  appe- 
tite and  is  drinking  a  pint  of  whiskey  daily.  The  bowels  are 
fairly  regular. 

Examination  May  6,  1914. — The  temperature  is  99:^5,  the 
pulse  no,  and  the  blood  pressure  195.  The  radials  are  not 
palpable.  The  apex  beat  is  normally  located  and  there  are 
no  adventitious  sounds,  excepting  an  accentuation  of  the 
aortic  sound.  The  lungs  are  negative.  The  tongue  is  coated 
in  the  center  and  red  and  sore  looking  along  the  sides;  the 
gums  are  sore  and  there  are  ulcer  patches  on  the  cheeks.  The 
liver  is  palpable  half  way  between  the  costal  margin  and  the 
umbilicus,  the  upper  border  being  normally  located.  The  knee 
jerk  is  absent,  the  pupils  normal,  and  the  Romberg  sign  is 
present.  The  eruption  on  the  backs  of  the  hands  is  symmetrical, 
extending  from  the  wrists  to  the  knuckles,  being  more  intense 
toward  the  radial  sides.  There  is  a  suppurating  area  on  the 
right  hand  near  the  base  of  the  index-finger.  The  urine  has  a 
specific  gravity  of  1,020,  acid  reaction,  contains  no  sugar  but 
an  abundance  of  albumin  and  some  bile;  microscopically  are 
seen  numerous  cylindroids  and  a  few  hyaline  casts;  the  hemo- 
globin is  90  per  cent,  and  a  stained  blood  film  is  negative. 


368  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

The  patient  was  started  on  small  daily  injections  of  iron 
cacodylate,  but  on  account  of  its  effect  on  the  urine  this  had 
to  be  discontinued  after  a  few  injections,  the  Hot  Springs  baths 
being  continued  daily.  On  May  25  a  diarrhea  began  which 
lasted  about  a  week.  By  June  2  the  hands  were  nearly  healed, 
Beck's  bismuth  paste  having  been  used.  The  mental  condi- 
tion was  normal  except  when  the  whiskey  was  diminished  a 
mild  delirium  supervened.  The  patient  continued  to  drink 
and  use  morphine  until  in  December,  1914,  he  was  committed 
to  an  institution  for  the  cure  of  those  habits.  After  his  release 
in  March,  1915,  he  remained  free  from  the  morphine  habit  but 
resumed  the  abuse  of  whiskey. 

The  only  symptom  which  reappeared  in  the  spring  of  191 5 
was  the  symmetrical  lesion  on  the  backs  of  the  hands,  and  at 
the  present  writing  the  patient  is  free  from  any  symptoms  of 
pellagra. 


CHAPTER  XXI 

DIAGNOSIS  OF  PELLAGRA 

Owing  to  the  fact  that  the  etiology  of  pellagra  is  unknown 
there  is  no  laboratory  procedure,  such  as  the  exaraination  of 
the  blood  for  a  parasite,  as  in  malaria,  or  the  feces  for  ova,  as 
in  hook-worm  infection,  which  will  aid  in  the  diagnosis.  So 
it  is  upon  the  symptomatology  past  and  present  that  the  phy- 
sician must  rely. 

The  diagnosis  of  this  disease  when  the  classical  symptoms — 
dermatitis,  stomatitis,  diarrhea  and  nervous  disturbances — are 
found  presents  little  or  no  difficulty,  but  it  is  in  those  cases  in 
which  some  of  the  above-mentioned  symptoms  are  absent  or 
which  are  complicated  by  other  diseases  that  try  the  acumen 
of  the  most  experienced  physician. 

One  of  the  most  important  factors  in  arriving  at  a  diagnosis 
in  pellagra  is  the  anamnesis,  which  should  be  most  thorough. 
If  no  eruption  or  evidence  of  past  eruption  is  present,  most 
diligent  inquiry  should  be  made  concerning  a  severe  sunburn 
or  burning  sensations  of  the  hands,  feet  and  face.  A  thorough 
investigation  should  be  made  into  a  history  of  sore  mouth, 
coated  tongue,  indigestion  and  diarrhea  if  these  symptoms 
are  not  present,  and  finally  a  thorough  interrogation  concern- 
ing abnormal  nervous  and  mental  states,  especially  depression 
and  excitability,  should  be  made. 

Skin  Lesions. — As  stated  above  the  most  frequent  location 
of  the  skin  lesions  of  pellagra  is  the  backs  of  the  hands,  and 
their  most  typical  feature  is  their  bilateral  occurrence,  and 
finally,  that  the  line  of  demarcation  is  most  clear  cut  between 
the  diseased  and  sound  skin;  and  while  the  erythema  does 
occur  on  any  part  of  the  body  surface,  the  diagnosis  of  pellagra 
would  be  unjustified  in  the  absence  of  the  symmetrical  lesions 
on  the  exposed  surfaces  of  the  body,  unless  other  symptoms 
are  most  marked. 

24  .  369 


370  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Menage'^^  considers  the  shriveling  and  furfuraceous  ex- 
foHation  of  the  horny  layers  of  the  epidermis  described  above 
as  absolutely  characteristic  of  pellagra,  whether  accompanied 
or  not  by  the  whole  symptom-complex. 

The  most  common  condition  which  must  be  differentiated 
from  the  pellagrous  eruption  is  the  erythema  of  sunburn.  The 
two  conditions  are  strikingly  similar,  the  pellagrous  lesion, 
however,  usually  being  darker  in  shade  than  the  sunburn. 
This  is  especially  noticeable  in  blonde  individuals.  The  sun- 
burn may  be  bilateral,  on  the  backs  of  the  hands,  and  the 
line  of  demarcation  most  distinct.  If  such  is  the  case,  in  the 
absence  of  other  symptoms  of  pellagra  a  diagnosis  cannot  be 
made  at  once,  and  the  future  course  of  the  erythema  must  be 
noted.  A  sunburn,  if  not  severe,  will  usually  fade  in  the  course 
of  a  few  days  leaving  nothing  more  than  a  slight  pigmentation, 
while  the  color  of  a  pellagrous  eruption  will  deepen  to  a  reddish- 
brown  or  chocolate  shade,  and  either  disappear  in  two  or  three 
weeks  with  exfoliation  of  the  epidermis  or  go  on  to  the  bullous 
state.  A  severe  sunburn  may  result  in  a  dermatitis  with  ves- 
icle formation,  and  present  an  impossible  problem  for  differen- 
tial diagnosis  from  pellagra  in  the  absence  of  other  symptoms. 

Eczema,  especially  of  the  vesicular  tjqoe,  might  be  mistaken  for 
pellagra,  but  is  differentiated  by  the  persistence  of  the  vesicles 
and  by  the  distinct  line  of  demarcation  in  the  latter  disease. 

Erythema  multiforme  often  presents  an  appearance  similar 
to  the  pellagrous  eruption  and  is  sometimes  most  difi&cult  of 
differentiation.  Here  again  the  symmetry,  the  line  of  demarca- 
tion and  the  symptoms  of  pellagra  not  referable  to  the  skin  will 
serve  as  distinguishing  features. 

Pellagra  may  be  differentiated  from  pityriasis  rubra  pilaris 
by  the  absence  of  itching  (usually),  the  configuration  and 
the  associated  symptoms. 

Not  infrequently  pellagra  may  be  mistaken  for  vitiligo,  es- 
pecially if  seen  during  exfoliation.  The  history  of  the  condition 
will  usually  clear  up  the  diagnosis,  as  vitiligo  is  as  a  rule  of 
insidious  growth  and  does  not  begin  with  an  erythema. 

The  common  roughening  of  the  skin  of  the  backs  of  the  hands 
frequently  seen  in  men  and  occasionally  in  women  who  are 


PELLAGRA  371 

continually  exposed  to  the  weather  has  been  mistaken  for  the 
pellagrous  eruption.  This  error  is  especially  likely  to  occur 
if  the  patient  is  suffering  from  stomatitis  or  diarrhea.  The 
absence  of  a  marked  line  of  demarcation  in  these  cases 
should  serve  as  a  distinguishing  feature. 

Acrodynia  is  mentioned  by  most  pellagrographers  as  a  disease 
which  may  be  mistaken  for  pellagra.  This  disease,  which  is  of 
obscure  origin,  begins  with  anorexia,  nausea,  vomiting  and 
diarrhea,  followed  by  swelling  of  the  face,  hands  and  feet,  and 
injection  of  the  conjunctivae.  Soon  symptoms  of  the  nervous 
system  develop,  such  as  prickling  and  burning  sensations.  In 
the  beginning  there  is  marked  hyperesthesia  of  the  extremities 
which  is  followed  by  anesthesia.  Severe  pains  in  the  extremities 
are  characteristic.  The  skin  manifestations  make  their  ap- 
pearance early  in  the  form  of  erythematous  spots,  first  on  the 
hands  and  feet,  especially  on  the  palms  and  soles,  and  later 
spread  to  the  arms  and  legs  and  even  to  the  trunk.  The 
portions  of  the  skin  affected  desquamate,  are  thickened  and 
brownish  and  may  even  take  on  a  black  pigmentation. 

It  usually  runs  a  favorable  course  of  one  or  two  month  3,  but  may 
be  fatal  in  debilitated  individuals  or  in  those  of  advanced  years. 

Acrodynia  should  not  present  much  difficulty  of  differentia- 
tion from  pellagra  owing  to  the  main  seat  of  the  eruption  (palms 
and  soles)  which  is  rare  in  the  latter  disease,  the  original  marked 
hyperesthesia  followed  by  anesthesia,  and  the  usual  short 
course  and  favorable  outcome. 

Pellagra  has  undoubtedly  often  been  mistaken  for  syphilis, 
especially  before  pellagra  was  recognized  in  this  country. 

The  characteristic  location  of  the  skin  lesions,  the  absence 
of  history  or  evidence  of  a  chancre  or  enlarged  glands,  and 
finally  the  negative  Wassermann  test  (certainly  in  the  vast 
majority  of  cases)  will  serve  to  differentiate  the  two  conditions. 

Scurvy  and  leprosy  have  been  mistaken  for  pellagra  and  vice 
versa  but  these  conditions  should  offer  little  or  no  difficulty  in  dif- 
ferentiating when  a  careful  history  and  examination  are  made. 

Gastro-intestinal  Symptoms. — There  are  very  few  conditions 
other  than  pellagra  in  which  the  classic  gastro-intestinal  symp- 
toms are  observed. 


372  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

In  sprue  is  found  a  gastro-intestinal  syndrome  which  in  many 
respects  very  closely  resembles  that  of  pellagra.  There  is 
more  or  less  stomatitis,  gastric  indigestion  with  distention  and 
diarrhea.  In  a  well-marked  case  of  sprue  it  is  impossible  to 
differentiate  the  stomatitis  from  that  of  pellagra  except  by 
observing  the  other  symptoms.  The  diarrhea  is  also  of  a 
similar  nature  to  that  of  pellagra,  except  that  it  maybe  the  stools 
are  more  copious  and  of  a  so-called  yeasty  consistence  and  the 
movements  occur  more  frequently  in  the  morning,  the  patient 
being  undisturbed  during  the  remainder  of  the  day.  This  is 
usually  not  the  case  in  pellagra,  where  the  diarrhea  is  as  marked 
during  the  afternoon  and  night  as  in  the  morning. 

Of  course,  where  a  characteristic  skin  eruption  exists  the  dif- 
ferential diagnosis  will  be  easy,  but  if  no  such  eruption  is  ob- 
served and  no  history  of  such  can  be  obtained,  in  short,  if  a  true 
pellagra  sine  pellagra  exists,  the  diagnosis  may  be  most  difficult. 

One  distinguishing  feature  which  may  be  of  value  is  the 
leucocyte  count  which  in  sprue  is  nearly  always  low  (6,000- 
2,800,  Castellani  and  Chalmers),  while  in  pellagra  it  is  usually 
increased.  Finally,  if  a  patient  with  pellagra  be  instructed 
to  sit  in  the  sun  for  a  couple  of  hours  with  the  backs  of  the 
hands  exposed  the  characteristic  eruption  will  usually  develop. 

Dysentery,  both  amebic  and  bacillary,  may  be  mistaken  for 
pellagra,  and  in  the  absence  of  skin  manifestations  in  the  latter 
may  present  some  difficulty  in  differentiation.  The  dysenteries 
usually  present  little  or  no  stomatitis,  and  as  a  rule  are  ac- 
companied by  more  or  less  rise  of  temperature. 

Of  course  the  finding  of  the  ameba  in  the  stools,  while  not 
proof  positive  that  the  patient  is  not  suffering  from  pellagra, 
in  the  absence  of  skin  manifestations  and  typical  mouth  find- 
ings, should  be  strong  presumptive  evidence  that  the  disease  is 
dysentery  without  pellagra  complication.  The  same  may  be 
said  of  the  cultural  isolation  of  the  dysentery  bacilli. 

It  is  possible  that  the  characteristic  odor  of  the  pellagrous 
stool  might  serve  as  a  differentiating  feature,  but  too  much 
stress  should  not  be  laid  upon  this. 

In  these  conditions,  again,  the  diagnosis  may  be  cleared  up 
by  placing  the  patient  in  the  sun. 


PELLAGRA  373 

Nervous  Symptoms. — Although  nervous  symptoms  develop 
in  a  large  percentage  of  cases  of  pellagra,  there  are  none  which 
are  typical  and  which  in  the  absence  of  other  findings  would 
justify  a  diagnosis.  Further,  they  are  usually  found  in  the 
later  course  of  the  disease  when  other  symptoms  will  be  manifest 
or  at  least  a  history  of  such  other  symptoms  may  be  obtained. 

Thus  we  find  disturbances  of  the  lower  tendon  reflexes,  ankle 
clonus,  tremors,  pain,  vertigo,  etc.,  in  many  other  conditions 
than  pellagra. 

Mental  S3miptoms. — From  what  has  been  written  in  the 
chapter  on  clinical  history  it  is  evident  that  there  is  no  typical 
mental  picture  in  pellagra,  that  we  may  have  symptomatic 
depressions  or  delirious  pictures  due  to  the  pellagrous  toxin  or 
toxins,  in  short,  intoxication  psychoses  which  are  in  no  way 
characteristic  of  pellagra  but  may  be  brought  about  by  other 
intoxications.  Further  that  certain  definite  psychoses,  manic- 
depressive  disorders,  dementia  prsecox,  paranoid  developments, 
etc.,  may  occur  in  certain  predisposed  individuals  with  the  pel- 
lagra acting  as  an  exciting  cause  but  in  no  way  differing  from 
these  conditions  in  non-pellagrins.  And  finally  certain  mental 
disorders  due  to  definite  brain  changes,  arteriosclerosis  dementia, 
senile  dementia,  presenile  psychoses  and  paresis,  may  be  present 
with  pellagra  merely  as  a  complication.  It  is  therefore  im- 
possible to  make  a  diagnosis  of  pellagra  on  the  mental  symp- 
toms alone,  and  even  in  the  presence  of  symptomatic  depression 
or  delirium  with  the  absence  of  other  pellagrous  symptoms  the 
examiner  must  look  for  another  cause  than  pellagra. 

It  should  here  be  reiterated  that  the  diagnosis  of  pellagra  on 
one  symptom  alone  usually  cannot  be  made,  that  the  whole 
history  and  clinical  findings  must  be  considered  and  a  diagnosis 
made  only  when  the  various  symptoms  can  be  reconciled  to  the 
symptom-complex  of  pellagra.  It  must  also  be  remembered 
that  pellagra  is  very  frequently  complicated  by  other  diseases, 
both  those  that  resemble  it  in  some  respects  and  those  that  do 
not,  which  condition  will  render  the  diagnosis  more  difficult. 


CHAPTER  XXn 
PROGNOSIS  OF  PELLAGRA 

Spontaneous  Recovery. — That  a  disease  so  protean  in  its 
manifestations  and  varying  so  in  the  degree  of  its  severity  may 
undergo  spontaneous  cure  is  not  beyond  the  range  of  possibility, 
although  we  are  unable  to  find  any  evidence  of  its  occurrence 
in  this  disease.  In  fact,  on  the  contrary,  Lavinder  and  Bab- 
cock^"^  state  that  untreated  pellagra  "  advances  inexorably  until 
finally  with  marked  involvement  of  the  central  nervous  system 
little  can  be  hoped  for  from  treatment." 

That  pellagra  may  vary  in  its  severity  in  different  localities 
and  the  prognosis  be  more  favorable  in  one  district  than  in 
another  is  undoubted.  It  has  for  some  time  been  considered 
by  most  American  observers  that  the  disease  in  this  country 
runs  a  more  fatal  course  than  in  Italy,  although  there  is  a 
tendency  at  the  present  time  among  American  pellagrographers 
to  consider  that  the  severity  of  the  disease  here  is  gradually 
decreasing. 

There  seems  to  be  some  difference  in  the  prognosis  of  pellagra 
in  various  races;  thus  Grimm-^-  graphically  shows  the  death 
rate  from  pellagra  in  the  negro  to  be  44.5  per  cent,  against  27 
per  cent,  in  the  white  race.  This  seems  to  us  to  be  more  on 
account  of  the  usual  differences  in  sanitation  between  the  two 
races  than  to  a  racial  difference,  for,  as  will  be  pointed  out  later, 
in  those  living  under  insanitary  conditions  the  prognosis  is 
worse  than  in  those  living  under  good  sanitary  conditions,  and 
as  the  negro  as  a  rule  lives  in  poorer  sanitary  surroundings  than 
the  white  we  would  expect  a  worse  prognosis  in  the  former. 

The  prognosis  of  pellagra  in  children  is  as  a  rule  good,  as  the 
disease  usually  runs  a  milder  course.  On  the  other  hand,  in 
elderly  people  the  prognosis  is  bad,  the  severity  of  the  disease 
depending  to  a  greater  or  less  extent  upon  the  debilities  of  the 
patient  incident  to  old  age. 

374 


PELLAGRA  375 

It  has  been  pointed  out  that  women  are  more  frequently 
affected  by  pellagra  than  men  and  the  death  rate  is  higher 
also.  According  to  Grimm^^-  the  death  rate  for  white  females 
is  28  per  cent,  and  white  males  26  per  cent.,  while  in  the  negro 
race  there  is  more  difference,  the  death  rate  for  females  being 
51  per  cent,  against  38  per  cent,  for  males. 

Occupation. — The  only  consideration  in  the  prognosis  in 
regard  to  occupation  of  the  individual  is  found  in  the  amount 
of  work  he  has  done.  Those  who  have  led  lives  which  have 
debilitated  them  to  a  more  or  less  extent  are  more  susceptible 
to  the  ravages  of  this  disease. 

As  stated  above,  the  prognosis  in  pellagra  is  less  favorable  in 
those  living  under  insanitary  surroundings,  and  as  this  condi- 
tion is  found  to  a  marked  degree  associated  with  poverty  it 
would  be  expected  that  in  those  of  poor  circumstances  the 
prognosis  would  be  worse  than  in  those  better  off.  Of  course 
it  may  be  contended  that  this  is  due  to  a  large  extent  to  the 
fact  that  those  of  affluent  circumstances  can  better  afford 
the  services  of  physicians  and  can  receive  better  nursing  than 
those  of  poorer  classes.  While  this  undoubtedly  is  true  to  a 
certain  extent,  it  would  seem  that  the  surroundings  of  the 
individual  with  regard  to  sanitation  have  more  bearing  upon 
the  subject. 

It  has  been  pointed  out  that  the  majority  of  cases  of  pellagra 
develop  in  the  spring  of  the  year,  and  it  is  also  a  fact  that  the 
advent  of  cold  weather  has  a  favorable  effect  upon  this  disease; 
therefore  it  would  seem,  although  we  have  no  figures  to  sub- 
stantiate this  statement,  that  cases  developing  in  the  fall 
would  have  a  better  prognosis  than  those  developing  in  the 
spring. 

That  the  occurrence  of  previous  diseases  in  an  individual  may 
have  a  bearing  upon  the  prognosis  of  pellagra  can  be  easily 
imagined.  It  has  been  pointed  out  above  that  pellagra  not 
infrequently  follows  such  diseases  as  typhoid  fever,  malaria, 
etc.,  and  it  would  seem  that  individuals  contracting  pellagra 
following  diseases  of  a  debilitating  character  would  give  a  less 
favorable  prognosis  than  those  in  whom  the  disease  developed 
without  previous  illness. 


376  ENDEMIC   DISEASES    OF    THE    SOUTHERN    STATES 

The  knowledge  of  the  habits  of  an  individual  is  of  more  or 
less  importance  in  making  a  prognosis.  Alcoholics  and  those 
who  have  indulged  in  venereal  excesses  are  of  necessity  less 
resistant  to  any  form  of  disease  than  those  who  have  lived  tem- 
perate lives,  and  therefore  in  the  former  class  of  individuals  the 
prognosis  is  more  grave  than  in  the  latter. 

It  is  natural  to  consider  that  the  complication  of  pellagra  by 
other  diseases  would  tend  to  make  the  prognosis  more  grave. 
This  is  indeed  the  case,  and  we  find  that  the  chances  for  recovery 
in  pellagra  are  less  when  this  disease  is  associated  with  other 
maladies. 

The  associated  infection  of  intestinal  parasites,  such  as  hook- 
worm and  amebae,  with  pellagra  undoubtedly  renders  the  prog- 
nosis more  grave,  partially,  at  least,  owing  to  infecting  organ- 
isms attacking  the  intestines  which  are  the  seat  of  so  much  of 
the  pathology  of  pellagra. 

Niles^"^  states  that  pellagra  when  found  in  hard  drinkers 
almost  invariably  runs  a  speedy  and  fatal  course.  This  un- 
doubtedly is  generally  true,  but  one  case  seen  by  one  of  us  is  an 
exception.  This  patient,  a  man  of  39  years  of  age,  developed 
the  symptoms  of  pellagra  in  the  spring  of  1914  with  the  char- 
acteristic findings — stomatitis,  diarrhea  and  dermatitis  on  the 
backs  of  the  hands.  He  was  at  that  time  consuming  a  quart 
of  whiskey  per  day  and  also  taking  25  to  30  grains  of  morphine 
in  the  twenty-four  hours.  Under  treatment  the  symptoms 
and  lesions  of  pellagra  cleared  up  with  only  a  slight  recurrence 
of  the  dermatitis  in  the  spring  of  1915,  which  lasted  but  a  short 
time  and  disappeared.  When  last  seen  he  was  still  consuming 
the  above-mentioned  amount  of  whiskey  and  had  no  evidence 
of  pellagra. 

The  complication  of  pellagra  by  tuberculosis,  whether  of  the 
lungs  or  of  other  portions  of  the  body,  is  nearly  always  rapidly 
fatal.  The  development  of  nearly  any  of  the  infectious  fevers, 
such  as  typhoid,  in  pellagrins  nearly  always  makes  the  prog- 
nosis extremely  grave. 

Most  observers  state  that  when  pellagrins  show  nervous  and 
mental  symptoms  the  prognosis  is  rendered  less  hopeful. 
This  undoubtedly  is  true  of  those  psychoses  due  to  the  pellagra 


PELLAGRA  377 

toxin  or  toxins,  the  symptomatic  depressions  and  delirious 
pictures,  and  also  no  doubt  of  those  psychoses  due  to  changes 
in  the  brain — arteriosclerotic  dementia,  senile  dementia,  paresis, 
etc. — and  perhaps  also  of  idiots  and  imbeciles  in  whom  pellagra 
develops,  but  we  do  not  believe  pellagra  associated  with  de- 
mentia praecox  or  paranoia,  for  example,  need  prove  any  more 
fatal  than  pellagra  in  normally  mental  individuals.  There  is 
one  exception  to  this  statement,  however,  and  that  is  the 
more  frequent  suicidal  intent  of  insane  individuals  than  those 
of  normal  mentality. 

The  prognosis  of  pellagra  in  pregnant  women  is  more  grave 
than  in  non-pregnant  women.  This  is  due,  partially,  at  least, 
to  the  liability  of  pregnant  pellagrins  to  abort  as  pointed  out 
above. 

The  gravity  of  the  skin  lesions  seems  to  have  little  or  no 
effect  on  the  prognosis,  those  with  the  most  severe  skin  mani- 
festations often  making  complete  recoveries.  This  is  more 
especially  true  of  the  "dry"  lesions,  as  the  "wet"  type  usually 
are  associated  with  more  serious  general  symptoms.  The 
appearance  of  so-called  typhoid  pellagra  is  to  be  considered  as 
of  most  grave  import,  as  most  cases  go  on  to  a  fatal  termi- 
nation. The  development  of  fever  in  the  course  of  the  disease 
presents  a  grave  condition  and  should  be  looked  upon  with 
concern. 

Continued  and  severe  diarrhea  is  one  of  the  gravest  symptoms 
as  it  usually  leads  to  marked  emaciation.  The  appearance  of 
nervous  symptoms  such  as  tremors,  absence  of  knee  Jerks,  ankle 
clonus,  etc.,  is  of  grave  import  and,  according  to  Wood,-"^  the 
appearance  of  a  coarse  clonic  contraction  of  the  muscles  of  the 
forearms  is  the  most  positive  indication  of  the  approaching 
end. 

As  in  nearly  all  other  diseases  the  prognosis  depends 
considerably  upon  the  promptness  of  the  diagnosis.  The 
earlier  the  diagnosis  the  earlier  treatment  may  be  insti- 
tuted, and  certainly  more  treated  cases  recover  than  un- 
treated ones. 

It  must  be  considered,  however,  especially  in  our  present 
state  of  knowledge  of  pellagra,   that  any  outbreak  of   this 


378  ENDEMIC   DISEASES    OF    THE    SOUTHERN   STATES 

disease,  no  matter  how  mild,  is  not  to  be  considered  lightly, 
and  that  the  most  diligent  methods  of  treatment  are  some- 
times of  no  avail. 

Mortality. — As  pointed  out,  the  death  rate  from  pellagra  in 
this  country  is  higher  than  in  Italy,  although  according  to  some 
observers  it  is  decreasing. 

Lavinder^^*  quoted  Lombroso  as  stating  that  in  1883  there 
were  treated  in  866  Italian  civil  hospitals  6,025  pellagrins  of 
whom  923  died,  while  in  1884. there  were  6,944  cases  treated 
in  993  hospitals,  790  dying,  making  in  a  large  number  of  cases 
a  death  rate  of  about  13  per  cent. 

Wollenberg^*^  reports  a  total  of  55,029  cases  of  pellagra  in 
Italy  in  1905  with  a  total  mortality  of  2,359,  which  is  a  little 
over  4  per  cent. 

Sandwith'"  states  that  of  his  cases  at  Kasr  el  Ainy  18  were 
cured,  72  relieved,  6  unrelieved  and  4  died,  making  a  mortality 
of  4  per  cent. 

Statistics  in  this  country  are  based  largely  upon  insane 
hospital  cases  in  which  the  mortality  is  very  high  in  spite  of 
the  fact  that  in  these  institutions  better  facilities  for  treatment 
are  usually  found  than  outside  them.  This  high  death  rate  of 
hospital  cases  is  no  doubt  due  to  the  fact  that  pellagra  cases 
do  not  as  a  rule  enter  hospitals  until  they  have  reached  the 
less  hopeful  stages  of  the  disease. 

According  to  the  Illinois  Pellagra  Commission, '^^  in  258  cases 
at  the  Peoria  institution  there  was  a  death  rate  due  to  the 
pellagra  per  se  of  49.6  per  cent. 

Searcy'°"  reported  88  cases  occurring  in  the  Mount  Vernon 
Insane  Hospital  in  1906,  of  which  57  or  64  per  cent.  died. 

Harrington^^^  states  that  of  32  cases  occurring  in  the  State 
Hospital  for  the  Insane  of  Rhode  Island  12  died,  giving  a 
mortality  of  37  per  cent. 

Of  the  91  cases  seen  by  one  of  us  at  the  Arkansas  State  Hos- 
pital for  Nervous  Diseases,  57  or  63  per  cent.  died. 

The  Thompson-McFadden  Pellagra  Commission^'^  gives 
the  following  table  of  cases  and  deaths,  as  far  as  could  be 
determined,  occurring  in  Spartanburg  County  from  1894  to 
191 2  inclusive: 


PELLAGRA 


379 


Year 

Number  of  deaths 

Number  of  cases      Per  cent,  of  deaths 

8l 

I 

I 

2 
2 
I 
I 
2 
14  . 

\ 

25 

114 

115 

28s 
376 

1898 

22 

1909 

28 

54 

47 

19 

This  shows  that  the  number  of  cases  is  increasing  but  the 
percentage  of  deaths  is  decreasing. 

Grimm^'-  of  a  total  of  1,426  cases  gives  a  death  rate  of  30.2 
per  cent.,  while  Lavinder^"*  reports  19,915  cases  with  8,085 
deaths,  or  a  mortality  of  40.59  per  cent. 

BealP^^  states  that  the  prevalence  of  pellagra  in  the  United 
States  is  decreasing,  although  he  estimated  the  death  rate  to 
be  over  25  per  cent. 


CHAPTER  XXm 
PROPHYLAXIS  OF  PELLAGRA 

The  methods  of  prophylaxis  proposed  for  pellagra  are  many 
and  are  based  to  a  large  extent  upon  the  theories  of  etiology 
as  upheld  by  those  proposing  them.  In  Italy,  where  the 
spoiled  maize  theory  is  almost  universally  accepted,  the  most 
thorough  and  extensive  prophylactic  measures  have  been  in- 
stituted with  this  theory  as  a  basis.  These  measures  are 
directed  against  the  sale  or  use  of  spoiled  corn. 

According  to  Sambon'^"  these  measures  are: 

1.  The  inspection  of  maize,  the  seizure  of  unsound  grain  and 
its  products. 

2.  The  exchange  of  deteriorated  maize  for  good  maize. 

3.  The  providing  of  drying  apparatus  for  damp  maize. 

4.  The  providing  of  suitable  ovens  in  rural  districts  for  the 
proper  baking  of  maize  bread. 

5.  The  abolition  of  late  varieties  of  maize  which  do  not  ripen 
properly. 

6.  The  compulsory  notification  of  all  cases  of  pellagra. 

7.  The  obligation,  in  all  affected  districts,  upon  the  municipal 
authorities  to  supply  free  meals  to  all  their  pellagrins  twice 
every  year  for  periods  of  not  less  than  forty  days. 

8.  The  institution  of  special  retreats,  "pellagrosari,"  for  the 
housing,  feeding  and  treatment  of  the  more  advanced  cases. 

9.  The  dispensation  of  free  salt  to  all  pellagrins  and  their 
families. 

This  author  continues  with  statistics  and  conclusions  of 
Professor  G.  Sanarelli,  Under-Secretary  of  State  for  Agriculture, 
of  Italy  who  claimed  that  beneficial  results  were  seen  almost 
immediately  after  the  application  of  the  law  of  1902,  stating 
that  the  pellagrins  within  the  kingdom  were  reduced  to  barely 
55,000  in  1905,  showing  a  reduction  of  over  17,000  in  the  last 
six  years.  Further  figures  by  Sanarelli  show  that  the  victims 
380 


PELLAGRA  381 

of  pellagra  in  Italy  in  the  three  years  1897-99  were  10,284; 
in  igoo-02  they  fell  to  9,219;  in  1903-05  they  declined  to  7,267; 
while  in  the  three  years  1906-08  the  number  was  only  4,649. 

More  comforting  to  Sanarelli  was  the  fact  that  in  1907 
4,950  new  cases  were  notified,  while  in  1908  only  2,846  were 
reported,  and  that  before  the  application  of  the  present  law  the 
yearly  mortality  from  pellagra  reached  or  exceeded  3,000,  while 
immediately  after  1902  the  number  of  deaths  only  just  exceeded 
2,000,  in  1907  were  1,635,  ^^^  i^  1908  were  only  about  1,000. 

The  conclusion  reached  is  that  these  measures  have  reduced 
the  number  of  pellagrins  by  50  per  cent.,  and  that  if  the  law  of 
1902  "had  only  been  fully  and  vigorously  enforced  in  all  the 
forty-four  provinces  of  the  kingdom  more  or  less  severely 
affected  by  the  fatal  disease,  at  this  hour  (1909)  the  whole  of 
Italy  would  be  entirely  free." 

Sambon  then  attempts  to  prove  that  instead  of  the  law  of  1902 
bringing  about  the  results  claimed  by  Sanarelli,  it  "failed  to 
produce  any  results  at  all."  He  states  that  the  decline  in  the 
number  of  cases  and  deaths  had  already  begun  in  a  very  striking 
manner  some  years  before  the  law  was  enacted,  and  further  that 
the  law  of  1902  did  not  come  into  effect  until  three  years  later. 
Then  Sambon  quotes  the  remarks  of  Sanarelli  made  upon  an- 
other occasion  in  which  he  directly  contradicts  himself,  after 
giving  statistics,  by  remarking:  "A  legitimate  doubt,  therefore, 
arises  as  to  whether  it  be  right  to  ascribe  the  gradual  decline 
of  pellagra  throughout  the  kingdom  to  the  measures  contained 
in  the  law  of  1902." 

Following  this  Sambon  goes  into  the  details  of  the  prophy- 
lactic propaganda  of  the  Italians  and  proves,  to  his  own  mind 
at  least,  that  they  have  failed  entirely  to  prevent  pellagra. 

While  the  bulk  of  evidence  is  against  the  theory  that  corn  is 
responsible  in  any  way  for  the  spread  of  pellagra  the  evidence 
is  negative,  and  certainly  no  other  theory  has  been  proven  cor- 
rect. And  further  since  spoiled  maize  is  unquestionably  not 
suited  for  human  consumption,  whether  or  not  it  has  anything 
to  do  with  pellagra,  an  effort  should  be  made  to  have  only  sound 
corn  used  for  food. 

While  Sambon  has  advanced  and  defended  the  theory  of  the 


382  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

transmissian  of  pel'lagra  by  the  Simulium,  he  has  not,  as  far  as 
we  are  aware,  proposed  any  definite  measures  of  prophylaxis. 

Wood,-'^  who  considers  this  theory  the  most  interesting  one 
at  this  time,  states  that  as  the  buffalo  fly  is  a  field  pest  its  control 
would  be  most  difficult  if  not  impossible.  However,  should  the 
Simulium  finally  be  proven  guilty  of  being  the  intermediary 
host  of  pellagra,  such  measures  as  screening,  destruction  of 
larvae,  etc.,  could  be  instituted.  The  spread  of  the  knowledge 
of  the  connection  of  this  insect  with  pellagra  would  in  itself 
make  those  who  come  into  contact  with  it  wary  of  its  bite  and 
certainly  lessen  the  number  of  cases. 

Should  the  stable  fly  {stomoxys  calcitrans)  prove  to  be  the 
intermediary  host,  as  suggested  by  Jennings  and  King,^^^ 
the  prophylaxis  of  pellagra  would  become  comparatively 
simple,  first  by  screening  and  second  by  the  destruction  of 
the  larvae  and  eggs  of  this  insect  in  manure. 

The  contagiousness  of  pellagra  has  been  discussed  in  the 
chapter  on  etiology,  and  as  no  evidence  has  been  produced  to 
show  that  this  disease  is  contagious  the  quarantine  or  isolation 
of  pellagrins  would  be  unwarranted  at  this  time.  However, 
owing  to  the  possibility  of  pellagra  being  infectious,  we  consider 
that  such  close  contact  as  kissing  of  pellagrins  should  be 
avoided,  and  further,  owing  to  the  rather  strong  evidence  that 
if  pellagra  is  an  infectious  disease  the  primary  location  of  the 
infecting  organism  is  in  the  gastro-intestinal  tract,  we  consider 
the  effective  disposal  of  the  excreta  of  pellagrins  of  importance. 
Also  we  consider  the  destruction  of  the  scales  and  flakes  of 
epidermis  which  come  from  the  skin  lesions  during  the  des- 
quamating stage  as  not  out  of  place.  At  least  such  proceedings 
can  work  but  little  hardship  upon  either  the  patient  or  his 
attendants  and  possible  sources  of  the  spread  of  the  disease 
will  be  removed. 

The  removal  of  secondary  or  alleged  predisposing  causes  of 
pellagra  in  endemic  districts  would  certainly  not  be  out  of 
place.  One  of  the  most  important  of  these,  as  pointed  out 
above,  is  alcoholism,  which,  even  if  it  is  not  a  predisposing  cause 
of  pellagra,  is  a  bane  upon  civilization  and  should  be  destroyed. 

Other  predisposing  causes  mentioned  are  other  previous  and 


PELLAGRA  "  383 

concomitant  diseases,  such  as  malaria,  typhoid,  hook-worm,  etc. ; 
so  measures  instituted  against  these  diseases  might  in  a  measure, 
at  least,  react  against  pellagra. 

The  theory  of  Allesandrini  and  Scala  that  pellagra  is  due  to 
certain  silica  compounds  contained  in  drinking  water,  while 
brilliant  in  conception,  lacks  confirmation.  If,  however,  it 
should  be  proven  correct,  the  prophylaxis  of  the  disease  would 
be  most  simple,  namely,  the  substitution  of  a  water  free  from 
these  substances. 

Goldberger,-^!  whose  deficiency  diet  theory  has  been  dis- 
cussed in  the  chapter  on  etiology,  states  that  "the  prevention 
and  eradication  of  pellagra  will  depend  essentially  upon  the 
substitution  of  a  mixed,  well-balanced,  varied  diet  for  the 
restricted,  one-sided  diet  that  the  individual  will  be  found  to 
have  consumed  prior  to  the  development  of  symptoms." 

He  further  states  that  the  amount  of  corn  or  other  starchy 
foods  should  be  reduced.  The  most  important  change  in  the 
diet,  however,  is  an  increased  consumption  of  fresh  (lean) 
meat,  milk,  eggs  and  legumes  ("beans  and  peas,  fresh  or  dried 
but  not  canned").  This  should  be  carried  out  especially  in 
the  late  fall,  winter  and  early  spring  months. 

The  poor,  especially  the  poor  of  the  South,  should  be  en- 
couraged to  cultivate  beans  and  peas  and  preserve  them  by 
drying  for  winter  consumption. 

Goldberger  states  that  at  orphanage  "B.  H."  there  were 
seventy-five  cases  of  pellagra  in  the  spring  of  19 13,  following  ap- 
parently milder  outbreaks  in  1911  and  1912.  A  modification  of 
the  diet  along  the  lines  mentioned  was  instituted  and  not  a  case 
was  known  to  have  developed  in  the  spring  and  summer  of  1914 
among  a  total  of  234  children  of  the  orphanage.  He  further 
states  that  there  is  reason  to  believe  this  experience  is  not  unique. 

In  the  insane  hospitals  care  must  be  taken  to  see  that  not  only 
is  a  well-balanced,  mixed  and  varied  diet  furnished  to  the 
patients,  but  that  they  actually  eat  it. 

Whether  or  not  Goldberger's  theory  is  proven  true,  we  con- 
sider his  tenets  as  to  diet  sound,  and  especially  in  the  absence  of 
proof  of  any  other  etiologic  theory  they  should  be  carried 
out. 


384  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

The  public  health  aspect  of  pellagra  assumes  the  proportions 
of  a  colossus.  The  disease  should  be  made  reportable  where 
it  is  not  so,  and  in  every  state  where  it  is  endemic  appropriations 
should  be  made  for  the  carrying  on  of  study  of  it;  not  only  an 
attempt  to  ascertain  the  etiology,  but  a  study  of  the  epidemi- 
ology, symptomatology,  prophylaxis  and  treatment  should  be 
made. 

The  laity  should  be  informed  of  what  we  already  know  of  the 
disease,  both  by  pamphlets  and  lectures,  and  should  be  en- 
couraged in  instituting  such  prophylactic  measures  as  are 
outlined  above. 


CHAPTER  XXrV 
TREATMENT  OF  PELLAGRA 

The  methods  of  treatment  of  pellagra  are  as  varied  as  are  the 
theories  of  its  etiology,  and  as  may  readily  be  imagined  many 
of  them  are  of  no  avail. 

The  methods  of  treatment  may  be  discussed  under  three 
headings,  namely:  hygienic  treatment,  specific  treatment 
(so  called),  and  symptomatic  treatment. 

Hygienic  Treatment. — The  first  requisite  in  the  treatment  of 
pellagra  is  that  the  patient  be  placed  under  sanitary  surround- 
ings. If  he  is  ambulatory  he  should  take  a  certain  amount  of 
exercise  daily,  but  should  avoid  the  direct  sunHght  except  in 
certain  nervous  and  mental  conditions  where  no  skin  lesions 
have  been  manifest  for  several  years,  in  which  sunlight  seems 
beneficial.  In  all  acute  cases  and  those  with  fever  the  patient 
should  be  put  to  bed,  in  which  case,  or  if  he  is  already  confined 
to  bed,  his  room  should  be  well  ventilated  but  with  the  light 
subdued.  It  goes  without  saying  that  bed  patients  should 
receive  the  best  of  nursing  and  their  beds  kept  clean  and  fresh. 
Change  of  climate  has  been  noted  by  many  observers  to  be  very 
beneficial  to  pellagrins,  the  change  from  a  warm  climate  to  a 
cold  one  being  most  recommended,  although  it  would  seem 
that  a  change  of  surroundings,  per  se,  is  helpful.  In  this 
connection  Bass^*-  has  recommended  an  artificial  refrigerated 
ward,  which  he  states  could  be  equipped  for  $3,000  and  main- 
tained at  an  expense  of  $1  per  day  per  patient  in  addition 
to  the  regular  expense. 

Hydrotherapy  of  various  forms  has  been  recommended  in 
pellagra.  Sufi&cient  bathing  for  cleanliness  is  of  course  to  be 
carried  out  in  all  cases. 

Other  hydrotherapy  must  be  governed  by  the  condition  of 
the  patient.  In  children  and  in  elderly  individuals  warm  baths 
should  be  employed.     In  weak  individuals  the  treatment  should 

2S  385 


386  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

be  begun  with  a  warm  bath  of  short  duration  and  the  tem- 
perature reduced  and  the  time  prolonged  with  the  improvement 
of  the  patient.  Massage  during  the  bath  is  often  beneficial. 
The  use  of  salt  baths  or  rubs  is  often  recommended,  from  which 
children  derive  the  most  benefit.  The  patient  should  be  placed 
in  a  tub  of  warm  water  and  after  the  body  is  wet  all  over  should 
stand  up  in  the  tub  and  the  attendant,  after  wetting  the  hands, 
takes  a  handful  of  salt  (any  good  fine  cooking  salt  will  do)  and 
thoroughly,  but  not  roughly,  rubs  the  entire  body  with  the 
salt  for  fifteen  to  twenty  minutes,  after  which  the  patient  Hes 
down  in  the  water,  the  salt  is  washed  off  and  if  the  patient  is 
sufficiently  robust  a  cold  douche  is  given,  after  which  he  is 
put  to  bed  for  a  time.  A  shower  bath  is  perhaps  more  satis- 
factory than  a  tub  for  this  purpose.  Medicated  baths  of  vari- 
ous kinds,  such  as  arsenic  and  sulphur,  are  some<:imes  used,  but 
are  of  doubtful  value. 

Baths  in  water  with  radio-activity,  such  as  at  the  Hot  Springs 
of  Arkansas  and  Virginia,  have  proven  beneficial  in  certain  cases. 
These  baths  should  of  course  be  controlled  by  the  condition  of 
the  patient,  and  should  be  given  in  conjunction  with  other 
methods  of  treatment. 

Whether  or  not  we  accept  the  teachings  of  Goldberger  con- 
cerning the  etiology  of  pellagra,  the  diet  he  recommends  as 
treatment  is  far  from  undesirable.  It  has  long  been  recognized 
that,  inasmuch  as  pellagra  is  usually  found  in  the  undernourished, 
one  of  the  first  and  most  essential  procedures  in  the  treatment 
is  to  prescribe  good,  wholesome,  and  nourishing  food. 

The  diet  recommended  by  Goldberger^^'  is  as  follows: 

Milk. — Fresh  milk,  alone  or  in  alternation  with  buttermilk, 
should  be  given  freely.  An  adult  should  be  urged  to  take  not 
less  than  a  pint  and  a  half  to  two  pints  in  twenty-four  hours. 

Eggs. — Fresh  eggs  should  be  allowed  freely.  In  addition 
to  the  milk  and  meat,  an  adult  should  take  not  less  than  four 
eggs  a  day.  In  certain  of  the  severer  forms  it  may  be  necessary 
to  give  the  eggs  in  the  form  of  albumin  water. 

Meat. — The  meat  should  be  fresh  lean  meat.  Whether  all 
fresh  meats  are  equally  valuable  in  treatment  we  do  not  know; 
future  studies  will  have  to  determine  this.     Our  experience  has 


PELLAGRA  387 

been  with  beef  alone.  This  may  be  served  as  scraped  beef, 
as  a  roast,  or  as  steak.  Where  mastication  is  painful,  meat 
juice  may  be  given  instead.  An  adult  should  be  urged  to  take 
at  least  a  half  pound  of  lean  meat  a  day  in  addition  to  the 
milk,  eggs,  and  legumes.  It  may  be  necessary  in  some  in- 
stances to  work  up  gradually  to  the  point  where  these  quan- 
tities can  be  taken. 

Legumes. — We  have  been  much  impressed  with  the  favorable 
results  following  the  use  of  beans  and  peas  alone.  The  beans 
and  peas  should  be  fresh  or  dried,  not  canned.  A  palatable 
pea  or  bean  soup  should  be  prepared  and  may  be  given  freely. 
In  addition  to  or  in  alternation  with  the  soup  the  beans  or  peas 
should  be  served  and  eaten  in  any  one  of  the  other  well-known 
forms. 

To  this  diet  of  Goldberger  we  feel  that  little  can  be  added. 
We  wish  to  say,  however,  that  in  view  of  the  absence  of  proof 
as  to  the  etiology  of  pellagra  and  out  of  deference  to  the  zeist 
theory,  although  we  do  not  subscribe  to  it,  we  are  accustomed 
to  advise  our  pellagra  patients  to  abstain  from  eating  corn  in 
any  form.  This  can  work  but  little  hardship  and  adds  an 
element  of  safety  until  the  exact  etiology  is  learned. 

Specific  Treatment. — The  so-called  specific  treatment  of 
pellagra  consists  of  the  empirical  administration  of  various 
medical  substances  upon  the  theory  that  they  are  specifics  for 
the  hypothetical  microorganism  of  the  disease;  the  practice  of 
transfusion  of  blood  and  the  administration  of  blood  serum 
from  cured  pellagrins  upon  the  theory  that  "antibodies" 
against  the  hypothetical  microorganism  are  being  introduced; 
and  finally,  the  practice  of  auto-serum  therapy. 

Lavinder  and  Babcock^"^  quote  Holland  as  having  written 
in  181 7:  "In  short,  it  appears  certain  that  mere  medicine  has 
done  very  little  for  the  relief  of  pellagra;  and  Strambio  frankly 
confesses  that  he  never  saw  a  case  distinctly  cured  by  the 
remedies  that  were  employed." 

These  writers  then  state  that  it  was  Lombroso  who  first  em- 
ployed arsenic  in  the  treatment  of  pellagra.  The  idea  of  the 
great  Italian  was  not,  however,  that  arsenic  is  a  true  specific 
for  the  disease,  that  it  did  not  cure  all  cases,  but  that  it  was  a 


388  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

valuable  remedy  acting  as  a  sort  of  antidote  for  the  toxins  of 
spoiled  maize.  Lombroso's  method  of  administration  of 
arsenic,  according  to  Lavinder  and  Babcock,  was  in  the  form 
of  Fowler's  solution  in  dosage  of  5,  10,  15,  20,  and  30  drops,  or 
as  pure  arsenous  acid  (arsenic  trioxide)  dissolved  in  slightly 
alcoholized  water,  in  doses  of  }io  to  }4o  milligram,  increasing 
according  to  tolerance  to  o.ooi,  0.002,  or  0.003  gram  and  very 
rarely  even  o.oi  gram.  The  drug  is  discontinued  for  a  few 
days  from  time  to  time. 

Lombroso  cautions  against  certain  untoward  effects  of  the 
arsenic  and  mentions  certain  types  of  the  disease  which  are 
benefited  by  the  treatment  and  certain  types  which  are  not. 
Symptomatic  and  dietetic  treatment  are  also  recommended  by 
the  Italians. 

Other  methods  of  administering  arsenic  in  pellagra  than  by 
mouth  have  been  employed  by  many  investigators.  Thus 
Babes,  according  to  Wood,^^^  was  the  first  to  use  atoxyl  in  the 
treatment  of  this  disease.  The  latter  writer  has  had  a  wide 
experience  in  the  use  of  this  drug,  recommending  its  use  in 
dosage  of  5  to  7  grains  every  fourth  day  in  the  beginning  and 
later  increasing  the  length  of  the  interval. 

The  untoward  effects  sometimes  seen,  such  as  chills,  faint- 
ing, headache, ^blindness  from  retrobulbar  neuritis,  colic,  loss 
of  appetite,  albuminuria,  etc.,  have  not  been  observed  by  Wood, 
although  expected  and  looked  for.  He  attributes  this  to  the 
careful  preparation  of  the  solution  of  the  drug  without  the  use 
of  heat  which  it  is  claimed  will  decompose  it.  Wood  reported 
very  favorably  upon  the  use  of  atoxyl,  but. stated  that  he  was 
instituting  the  use  of  soamin  because  it  is  said  to  be  less  toxic. 

Soamin  has  been  used  very  extensively  by  many  investigators 
with  more  or  less  satisfactory  results.  Martin^^^  reported  its 
use  in  six  cases  of  pronounced  pellagra  and  five  of  suspected 
pellagra.  In  the  latter  the  suspicious  symptoms  were  promptly 
relieved  by  a  few  injections  of  soamin,  and  of  the  six  pronounced 
cases  all  but  one,  who  died  within  a  week  after  the  institution  of 
treatment,  made  apparent  recoveries.  Martin  injected  this 
drug  in  3-  to  s-grain  doses  on  alternate  days,  giving  100  grains 
as  a  maximum  for  one  course  of  treatment. 


PELLAGRA  389 

Probably  no  other  drug  has  ever  received  the  attention  that 
Ehrlich's  saharsan  or  "606"  has,  and  it  is  natural  to  suppose 
that  a  drug  which  contains  arsenic  and  is  said  to  be  less  toxic 
than  any  other  so  far  produced  should,  in  view  of  the  results 
obtained  with  other  arsenical  preparations,  be  given  a  trial 
in  pellagra. 

As  far  as  we  are  able  to  determine,  Nice,  McLester  and  Tor- 
rance'*^ were  the  first  to  report  on  the  use  of  salvarsan  in  the 
treatment  of  pellagra.  These  workers  reported  apparent  re- 
coveries in  three  cases. 

Cole  and  Winthrop'*''  collected  the  reports  of  twenty-one 
cases  of  different  investigators  with  only  33 J  3  per  cent,  im- 
provement lasting  seven  or  more  days. 

King  and  CrowelP**  reported  nineteen  cases  in  which  as  a 
rule  three  doses  of  salvarsan  were  administered  ten  days  apart 
with  apparent  recoveries  in  all  but  one  case. 

Cranston'^^  administered  salvarsan  to  eleven  pellagrins  in 
1911  with  the  following  rather  discouraging  results:  Two  left 
the  hospital  clinically  cured;  one  was  considered  well  until 
nausea  developed  a  few  days  before  the  report  was  made  and 
was  therefore  considered  suspicious;  three  relapsed  and  were 
treated  a  second  time;  one  was  unimproved  and  four  died. 

Probably  the  most  enthusiastic  supporter  of  salvarsan  in 
the  treatment  of  pellagra  is  Martin'^*  who  considers  this  drug 
a  true  specific  for  the  hypothetical  microorganism  of  the  dis- 
ease. This  investigator  has  used  salvarsan  in  a  great  many 
cases  (he  does  not  state  how  many)  and  contends  that  one  may 
confidently  expect  to  cure  over  80  per  cent,  of  cases  by  the  use 
of  soamin  or  salvarsan  or  both. 

Martin's  method  of  procedure  is  to  administer  salvarsan 
intravenously  in  doses  of  o.i  gram  per  20  pounds  of  weight, 
at  weekly  or  ten-day  intervals  until  no  so-called  endotoxin 
reaction  occurs.  He  claims  perfect  cures  in  favorable  cases 
(he  states  he  is  unable  to  say  why  favorable)  after  three  or  four 
doses,  but  considers  that  six,  eight  or  ten  doses  will  usually  be 
required.  Martin  states  that  occasionally  salvarsan  seems  to 
cause  a  recrudescence  of  the  disease,  and  that  several  days 
following  the  first  or  second  dose  the  mouth  becomes  red,  diar- 


3 go  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

rhea  begins  and  new  skin  lesions  occur.  This,  Martin  thinks, 
is  an  indication  that  a  specific  drug  has  been  used,  though  in 
insufficient  dosage. 

In  a  comparatively  small  experience  with  salvarsan  in  the 
treatment  of  pellagra  we  are  forced  to  the  conclusion  that  it 
does  not  act  as  a  specific.  One  case  treated  by  one  of  us  in  the 
spring  of  1911  is  very  much  to  the  point. 

This  patient,  a  man  of  forty-nine  years,  had  suffered  with  diar- 
rhea for  two  summers,  accompanied  by  a  breaking  out  on  the 
backs  of  the  hands.  When  examined  there  was  a  characteristic 
eruption  on  the  backs  of  the  hands  extending  about  4  inches  up 
the  forearm.  Marked  diarrhea  was  present,  there  being  an 
average  of  fifteen  bowel  movements  per  day.  Three  doses  0.6 
gram  of  salvarsan  were  administered  intravenously  ten  days 
apart  with  absolutely  no  improvement.  The  patient  grew 
steadily  worse  and  died  three  weeks  after  the  administration 
of  the  last  dose  of  salvarsan. 

We  are  of  the  opinion  that  arsenic  in  any  form,  which  exerts  no 
untoward  effect,  is  to  be  recommended  in  pellagra.  This  we 
do  not  consider  as  acting  so  much  in  the  nature  of  a  specific 
as  in  the  nature  of  a  tonic  and  alterant,  although  we  are  not 
prepared  to  say  that  it  does  not  have  specific  action.  We  have 
found  that  sodium  cacodylate  has  given  the  best  results  in  our 
hands.  This  is  administered  intramuscularly,  usually  in  3- 
grain  doses  daily.  The  dosage  may,  however,  be  increased,  we 
having  given  as  high  as  9  grains  daily  without  any  untoward 
effects. 

A  number  of  investigators  have  reported  favorable  results  from 
the  use  of  hexamethylamine.  Other  drugs,  sodium  chloride, 
gelsemium,  potassium  permanganate,  thyroid  extract,  calcium 
sulphide,  castor  oil,  nitric  acid,  opium,  etc.,  have  had  their 
advocates,  but  do  not  seem  to  offer  much. 

Dyer^'^  advocates  very  strongly  the  use  of  quinine  hydro- 
bromate  and  considers  it  as  much  of  a  specific  as  any  drug  so 
far  proposed.  It  is  given  in  doses  of  2  to  5  grains  three  times 
a  day  in  mild  cases,  and  as  much  as  10  grains  every  two  to  three 
hours  in  severe  cases.  Dyer  states  that  he  has  given  as  much 
as  10  grains  every  three  hours  night  and  day  for  four  to  five 


PELLAGRA  391 

days  and  that  he  has  never  lost  a  case  of  pellagra  treated 
entirely  and  throughout  by  himself. 

Recently  Page^-"  has  advocated  the  use  of  ichthyol,  and 
states  that  one  or  two  5-grain  pills  three  or  four  times  a  day 
for  three  weeks  seems  to  cure  the  average  case. 

We  have  had  experience  with  this  drug  used  in  this  manner 
in  but  one  case,  but  have  been  informed  that  at  the  Arkansas 
State  Hospital  for  Nervous  Diseases,  it  was  used  in  several  cases 
with  apparently  no  beneficial  results. 

According  to  Cole  and  Winthrop^^^  Antonini  and  Marianni 
secured  curative  results  in  pellagra  by  the  injection  of  blood 
serum  from  cured  pellagrins. 

Cole^'"  early  in  1909  published  the  results  of  blood  trans- 
fusion from  a  cured  pellagrin  into  a  case  which  was  considered 
absolutely  hopeless,  but  which  completely  recovered. 

In  1910  Cole  with  Winthrop^^^  reported  six  recoveries  in 
eleven  cases.  These  investigators  considered  that  if  the  blood 
serum  of  cured  pellagrins  contained  specific  antibodies  the  whole 
blood  would  also  contain  them,  as  well  as  help  replenish  the 
impoverished  blood  stream  of  the  patient.  They  point  out 
four  dangers  of  transfusion,  aside  from  the  technic  difficulties, 
as  follows:  the  transmission  of  disease,  hemolysis,  agglutination 
and  acute  dilatation  of  the  heart. 

Later  these  workers"^  reported  twenty  cases  of  pellagra  in 
whom  transfusion  was  performed  with  twelve  recoveries.  At 
this  time,  however,  they  stated  that  it  seemed  to  make  no 
difference  whether  the  donor  was  a  cured  pellagrin  or  any  other 
healthy  individual. 

According  to  Castellani  and  Chalmers^^-  a  most  unique 
method  of  treatment  has  been  devised  by  Nicolaidi.  This 
consists  of  horse-serum  together  with  all  the  organic  and  mineral 
salts  of  the  blood,  in  a  solution  saturated  with  carbon  dioxide 
gas,  which  is  then  rendered  radioactive.  The  preparation  is 
administered  by  injections  until  twenty  or  twenty-five  are 
given.  Neither  dosage  nor  the  method  of  injection  is  stated. 
Remarkable  improvement  is  reported  by  Nicolaidi  and  accord- 
ing to  Castellani  and  Chalmers  his  results  are  supported  by 
several  eminent  authorities. 


392  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Palmer  and  Secor"^  after  a  short  review  of  the  literature  of 
auto-serotherapy  in  other  diseases  report  the  treatment  of  seven 
cases  of  pellagra  by  this  method  with  most  gratifying  results. 
Two  cases,  according  to  these  authors  are  well,  having  passed 
a  spring  and  fall  season  without  recrudescence  of  the  disease. 
Two  others  are  apparently  well  but  as  yet  have  not  passed  the 
critical  seasons,  while  the  other  three  showed  marked  improve- 
ment but  have  been  lost  track  of. 

The  technic  employed  is  to  apply  a  piece  of  cantharides 
plaster  ij-^  inches  square,  smeared  with  olive  oil,  to  the  chest 
at  bedtime.  In  the  morning  a  blister  will  be  raised.  Without 
entirely  removing  the  plaster  a  hypodermic  needle  is  thrust 
into  the  blister  from  an  upper  corner,  i  c.c.  of  serum  withdrawn 
and  injected  into  the  arm.     No  visible  reaction  should  occur. 

Palmer  and  Secor  state  that  their  therapy  is  based  upon  the 
theory  that  the  beneficial  effects  derived  from  the  old-time 
blister  in  pneumonia  were  not  entirely  due  to  the  counter- 
irritation  but  that  antigens  were  produced  in  the  serum  and 
reabsorbed,  thus  stimulating  the  production  of  antibodies. 

We  have  seen  this  method  tried  in  one  case  with  apparently 
good  results,  although  this  patient  Avas  at  the  same  time  under 
treatment  with  sodium  cacodylate.  We  consider  this  treatment 
rational  and  as  it  is  very  simple  and  devoid  of  much  pain  and 
discomfort  to  the  patient,  should  be  given  a  thorough  trial. 

Instead  of  cantharides  plaster,  however,  we  recommend  the 
application  of  cantharides  collodion. 

Symptomatic  Treatment. — The  skin  lesions  are  treated 
according  to  their  severity,  and  it  is  best  to  err  on  the  side  of  too 
little  treatment  rather  than  too  much.  In  the  beginning  when 
there  is  nothing  but  an  erythema  a  dressing  of  boric  acid  solu- 
tion is  quite  sufficient.  Later  when  the  eruption  has  started 
to  desquamate  zinc  oxide  ointment  should  be  applied.  The 
main  requisite  in  this  condition  to  our  minds  is  to  exclude  the 
light,  for  which  purpose  zinc  oxide  has  been  found  by  one  of  us 
best  suited.  By  coating  photographic  plates  with  various 
substances,  zinc  oxide,  ichthyol,  bismuth  subnitrate  and  bella- 
donna ointment,  exposing  them  to  the  light  for  several  minutes, 
removing  the  coating  and  developing,  those  covered  with  the 


PELLAGRA  393 

zinc  oxide  showed  almost  absolute  exclusion  of  the  light  while 
the  other  substances  permitted  more  or  less  light  to  penetrate. 
For  the  so-called  "wet"  lesions  ordinary  surgical  treatment 
should  be  employed.  Moist  dressings  of  bichloride  (i  to  5,000) 
or  I  per  cent,  p  eric  acid  are  good.  If  there  is  secondary  in- 
fection with  pyogenic  organisms  the  parts  should  have  hydrogen 
peroxide  applied  in  dilute  solution  once  daily  and  aristol  or 
some  similar  powder  dusted  over  them. 

Of  the  gastro-intestinal  symptoms  the  anorexia  and  nausea 
are  usually  relieved  by  nux  vomica,  condurango  or  some  other 
bitter.  Leroy^^^  has  recommended  a  mixture  of  cerium  oxalate, 
chloretone  and  bismuth   subnitrate  in  troublesome  vomiting. 

For  the  stomatitis  if  ulceration  exists  daily  application  of 
silver  nitrate  solution  (4  per  cent.)  will  be  of  benefit.  An  as- 
tringent mouth  wash  such  as  the  following  should  be  used: 

^.     Potassii  chloratis 3ii 

Tinct.  myrrhse f  5  ss 

Mellis  depurati f  S  ss 

Aquas  camphors q.s.  ad  fSviij 

Sig. — Shake;  use  as  mouth  wash,  t.i.d. 

If  salivation  exists  atropin  J  200  grain  every  four  hours  until 
checked,  may  be  used. 

For  the  gastric  symptoms  when  there  is  a  deficiency  of  hy- 
drochloric acid,  this  drug  may  be  administered  10-15  drops  of 
the  official  dilute  t.i.d.  after  meals.  Pepsin  also  may  be 
given. 

Many  drugs  have  been  advocated  for  the  diarrhea,  bismuth 
in  some  form  being  most  frequently  used.  Ergot,  albumin 
tannate,  and  salol  are  also  extensively  employed. 

j)ygj.373  states  that  the  quinine  hydrobromate  he  recom- 
mends as  a  specific  will  control  the  diarrhea  usually  within  the 
first  five  days.  Tablets  of  B.  bulgaricus  have  been  used  by  one 
of  us  for  the  control  of  the  diarrhea  but  without  very  flattering 
results. 

When  all  other  means  fail  opium  in  some  form  may  be  given. 

Where  constipation  is  present  instead  of  diarrhea  it  may  best 
be  controlled  by  castor  oil.  Phenolphthalein  or  sodium  phos- 
phate may  also  be  employed. 

Of  the  nervous  symptoms  insomnia  will  usually  be  overcome 


394  ENDEMIC   DISEASES   OF   THE    SOUTHERN    STATES 

by  the  administration  of  chloretone  in  doses  of  3  to  5  grains. 
Trional,  veronal  or  sulphonal  may  be  used.  For  the  pains  and 
burning  sensation  phenacetin,  aspirin  or  some  other  salicylate 
may  be  administered. 

The  various  mental  symptoms  can  be  treated  satisfactorily 
only  in  a  hospital  for  the  insane.  The  depressed  conditions 
improve  with  the  general  condition.  For  the  delirium  small 
doses  of  deodorized  tincture  of  opium  is  best. 

The  other  mental  conditions  associated  with  pellagra  but 
not  directly  due  to  the  toxins  must  be  treated  as  if  the  pellagra 
were  not  present. 

An  important  part  of  the  treatment  of  pellagra  is  that  which 
is  carried  out  between  attacks.  The  patient  should  be  under 
observation  and  the  general  condition  should  be  made  as  good 
as  possible,  with  careful  diet,  exercise,  tonics,  etc.  A  careful 
record  of  the  weight  should  be  kept  as  the  season  approaches 
for  the  attack,  the  development  of  slight  symptoms  should  be 
noted  and  treated  at  once.  If  possible  a  change  to  a  colder 
climate  is  highly  to  be  recommended. 

It  goes  without  saying  that  concomitant  diseases  should 
be  recognized  and  treated.  Thus  in  the  advent  of  malaria, 
quinine  should  be  given,  hook-worm  should  be  treated  with  salol, 
and  cases  with  amebiasis  should  receive  emetine.  All  major 
surgical  procedures,  except  those  absolutely  necessary,  should 
be  postponed  until  the  symptoms  of  pellagra  subside. 


AMEBIC  DYSENTERY 


CHAPTER  XXV 
INTRODUCTION 

Amebic  dysentery  is  an  infectious  disease,  caused  by  a  specific 
protozoal  microorganism,  the  Endamceba  histolytica,  charac- 
terized clinically  by  abdominal  pain,  diarrhea  and  tenesmus, 
anatomically  by  ulceration  of  the  colon,  sigmoid  and  rectum, 
with  a  tendency  to  recurrences  and  chronicity  and  to  the  forma- 
tion of  hepatic  abscess. 

Amebic  dysentery  is  also  known  as  amebic  enteritis,  amebic 
colitis,  amebiasis,  tropical  dysentery,  amobenruhr,  dysenteric 
amibienne  and  dysenterie  a  amibes. 

History. — The  history  of  amebic  dysentery  may  well  be 
said  to  begin  with  Lambl"*  who  in  1859  discovered  a  minute, 
motile,  unicellular  organism  in  the  intestinal  mucus  removed 
at  necropsy  of  a  child  dead  of  diarrhea.  Lambl  described  the 
organism  as  being  roughly  spherical  in  shape  when  at  rest,  of 
0.009  mm.  by  0.016  mm.  in  size,  but  assuming  an  elongated 
shape  when  in  motion.  Motility  was  attained  by  throwing  out 
club-shaped  pseudopodia  which  were  of  the  same  substance 
as  the  body.  Lambl  observed  vacuoles  in  the  body  of  the  pro- 
tozoon  and  occasionally  very  minute  ones  in  the  nucleus.  The 
peculiar  vibration  of  the  granules  in  the  protoplasm  was  noted. 
Both  classes  of  movement  were  stated  by  this  investigator  to 
be  very  marked  at  first  but  to  cease  gradually  within  a  few  hours. 

While  Lambl  did  not  definitely  incriminate  the  organism  he 
described  as  the  cause  of  dysentery  he  did  state  that  its  impor- 
tance should  not  be  underrated. 

The  importance  of  Lambl's  work  was  unrecognized  and  in 
1870  Lewis  and  Cunningham^''^  described  quite  fully  certain 
amebas  found  in  the  feces  of  cholera  patients  but  ascribed  to 
them  no  pathologic  significance. 
395 


396  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

In  1875  Loesch'^^  published  an  account  of  the  findings  of 
ameba  in  the  feces  of  a  patient  with  dysentery.  This  patient 
had  been  suffering  intermittently  with  the  disease  for  two  years 
and  finally  succumbed.  Just  before  death  the  organisms  were 
absent  from  the  feces  but  were  found  at  necropsy  in  great  num- 
bers in  the  intestinal  contents  and  in  ulcers  of  the  colon  and 
sigmoid.  Loesch  also  did  not  definitely  incriminate  the  amebse 
as  the  cause  of  the  disease,  considering  that  they  possibly 
merely  aggravated  the  condition.  Nevertheless  he  injected 
rectally  four  dogs  with  some  mucus  containing  amebffi,  produc- 
ing in  one  instance  a  dysentery,  recovered  the  amebse  from  the 
feces  and  found  ulceration  in  the  lower  colon. 

Grassi^'^  also  found  amebee  in  the  feces  of  dysenteric  patients 
as  well  as  in  normal  individuals.  He,  therefore,  considered  them 
as  non-pathogenic.  This  worker  described  a  cystic  stage  of 
the  amebse  which  occurred  more  frequently  when  the  organ- 
isms were  forced  to  live  under  unfavorable  circumstances. 

Following  the  work  of  Grassi  numerous  investigators  re- 
ported the  finding  of  amebee  in  the  feces  of  both  normal  persons 
and  those  suffering  from  dysentery  (Leuckart,^^"  Sonsino,^^^ 
Perroncito^^^). 

Koch'^'  in  1883,  while  studying  cholera  in  Egypt  described 
amebae  as  occurring  in  sections  of  the  intestinal  walls.  While 
Koch  considered  these  as  of  possible  pathologic  significance 
owing  to  his  other  investigations  he  did  not  pursue  the  work 
further  at  that  time. 

However,  stimulated  by  the  work  of  Koch,  Kartulis'^*  under- 
took extensive  investigations  of  this  important  subject  and 
added  greatly  to  the  knowledge  concerning  it.  This  worker 
found  the  amebs  in  many  cases  of  dysentery  both  during  life 
and  at  autopsy  and  failed  to  find  them  in  cases  of  typhus, 
typhoid,  tuberculosis  and  Bilharzia  disease.  He  therefore 
rightly  concluded  that  the  amebse  were  the  cause  of  the  disease. 
He  attempted  to  cultivate  the  organism  and  to  reproduce 
the  disease  in  guinea-pigs  but  without  success.  He,  however, 
showed  the  relationship  of  hepatic  abscess  to  the  amebas. 

The  findings  of  Kartulis  were  very  quickly  confirmed  by 
several  investigators. 


AMEBIC    DYSENTERY  397 

Hlava'^'^  in  Prague  found  the  organism  in  sixty  cases  of 
dysentery  and  was  able  to  produce  the  disease  in  cats  and 
dogs  by  injection  into  the  rectum  of  feces  containing  amebas. 

The  first  worker  in  America  to  report  the  finding  of  amebas  in 
dysentery  was  Osler^^^  who  in  1890  discovered  these  organisms 
in  the  feces  and  pus  from  an  hepatic  abscess  of  a  patient  who 
had  returned  from  Panama. 

In  a  short  time  Musser'^*^  reported  four  cases  and  StengeP'* 
three  from  Philadelphia,  while  Dock^*'  found  amebse  in  twelve 
cases  of  acute  and  chronic  dysentery  in  Galveston,  which  were 
the  first  reported  from  the  South. 

In  1 89 1  Councilman  and  Lafleur'^"  published  a  most  com- 
plete description  of  the  disease  with  a  critical  study  of  the 
literature.  These  authors  concluded  that  a  disease  entity  with 
definite  pathologic  findings  was  produced  by  the  amebje  and 
proposed  the  name  "Amoeba  dysenterise"  for  the  organism. 
They,  however,  considered  that  other  amebse,  perhaps  non- 
pathologic  might  be  found. 

The  work  of  Councilman  and  Lafleur  created  a  stir  both 
among  zoologists  and  physicians  and  an  extensive  literature 
quickly  sprang  up,  some  investigators  accepting  the  work  and 
others  rejecting  it. 

Maggiora'^'  in  1893  after  reviewing  the  evidence  at  hand 
reached  the  conclusion  that  the  ameba  coH  could  not  be  con- 
sidered as  the  cause  of  any  kind  of  dysentery. 

Gasser'^-  injected  garden  mould  into  cats  producing  a  colitis 
and  recovered  amebae  from  their  feces  apparently  identical  with 
those  of  Loesch  and  Kartulis. 

However,  Quincke  and  Roos^^^  confirmed  the  work  of  Council- 
man and  Lafleur  and  concluded  that  there  were  three  varie- 
ties of  amebse,  one  being  very  virulent  and  causing  a  marked 
dysentery,  another  being  less  virulent  and  causing  only  a  mild 
dysentery,  while  the  third  was  non-pathogenic.  Their  conclu- 
sions were  partially  based  upon  experimental  evidence,  their 
first  organisms  producing  marked  symptoms  when  injected  into 
the  rectum  of  cats  while  the  other  organisms  so  injected  pro- 
duced no  symptoms. 

Kruse  and  Pasquale,^'*  working  in  Egypt,  also  confirmed  and 


398  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

extended  the  work  of  Councilman  and  Lafleur,  finding  a  patho- 
genic and  non-pathogenic  type  of  ameba  in  the  intestine.  They 
also  produced  dysentery  in  cats  by  the  injection  of  pus  from  an 
hepatic  abscess  bacteriologically  sterile,  but  containing  amebse, 
into  the  rectum. 

During  the  next  ten  years  numerous  investigators  contributed 
to  the  study  of  the  intestinal  amebae  of  man,  but  it  was  left 
for  the  zoologist,  Schaudinn,  whose  name  will  be  immortal  as 
the  discoverer  of  the  specific  organism  of  syphilis,  to  differentiate 
scientifically  the  pathogenic  and  the.,  non-pathogenic  species. 
The  former  he  termed  Entamozha  histolytica  and  showed  it  to 
be  the  definite  cause  of  amebic  dysentery,  while  the  latter  was 
designated  Entamceba  coli.  However,  it  would  seem  that  the 
term  Endamceba  is  the  more  correct  as  Leidy^'^  as  far  back  as 
1879  estabHshed  the  genus  Endamceba  for  parasitic  amebas. 
Schaudinn's  untimely  end  was  probably  brought  about  as  a 
result  of  his  investigations  into  the  amebs  as  he  allowed  himself 
to  become  infected  by  swallowing  the  developmental  cysts 
of  the  organisms  and  suffered  with  intermittent  attacks  of 
dysentery  until  the  time  of  his  death  in  1906  following  suppura- 
tion around  the  sigmoid. 

Schaudinn's  work  was  confirmed  by  many  writers,  among 
them  Craig, ^^^  Sandby  and  Miller, ^^^  Kartulis^®'  and  others. 

In  1906  Viereck^^^  described  an  organism  that  he  considered 
a  third  species  and  termed  it  Endamceba  ietragena.  This  he 
thought  the  cause  of  a  certain  form  of  dysentery,  but  by  most 
investigators  Viereck's  ameba  is  considered  identical  with  the 
endamceba  histolytica. 

Numerous  other  workers  have  described  amebas  which  they 
considered  as  distinct  species,  but  their  findings  have  not  been 
confirmed  and  are  considered  by  most  authorities  as  based  upon 
insufficient  evidence  and  that  they  will  eventually  be  shown  to 
belong  either  to  the  species  of  Endamceba  histolytica  ox  Endamceba 
coli. 

Geographic  Distribution. — The  distribution  of  amebic  dys- 
entery is  widespread  although  as  with  most  infectious  diseases 
there  are  certain  endemic  centers  in  which  it  is  found  more 
prevalent  than  in  others. 


AMEBIC    DYSENTERY  399 

In  Europe  the  disease  is  less  prevalent  than  in  some  of  the 
other  continents.  It  is  endemic,  however,  in  parts  of  Italy, 
Malta,  Sicily  and  in  the  Balkans.  It  has  been  observed  more 
or  less  frequently  in  Austria,  Hungary,  Germany  and  Russia. 
In  1901  Jagers^'^  reported  an  epidemic  among  the  German 
troops  of  East  Prussia.  In  England^'*  and  France  sporadic  cases 
have  been  reported  from  time  to  time,  some  of  them  in  in- 
dividuals who  have  never  been  out  of  their  native  countries. 
We  are  unable  to  find  the  reports  of  any  cases  occurring  in  the 
Scandinavian  countries. 

Many  hot  beds  of  amebic  dysentery  exist  in  Asia.  Thus  in 
southern  China,  India  and  Siam  it  is  found  most  prevalent,  but 
in  northern  and  central  China  and  Japan,  while  dysentery  is 
found,  the  bacillary  type  is  more  frequent. 

In  the  East  Indies  and  the  Philippines  are  found  extensive 
endemic  centers. 

Africa  is  found  to  contain  many  endemic  centers  of  amebic 
dysentery.  In  Egypt  along  the  lowlands  of  the  Nile  it  is  prob- 
ably found  more  frequently  than  in  any  other  country  of  the 
world,  although  in  the  upper  portion  of  the  country  it  is  rare. 
It  is  found  in  the  Mediterranean  countries,  Morocco,  Tunis  and 
Algiers,  while  in  South  and  Central  Africa  it  is  more  or  less 
rare.  In  Australia  and  Polynesia  it  is  endemic,  and  is  of 
frequent  occurrence. 

In  South  America,  amebic  dysentery  is  found  quite  frequently 
in  Chili,  Brazil,  and  Venezuela,  but  less  often  in  the  southern 
countries. 

Central  America,  Panama  and  Mexico  contain  many  endemic 
centers. 

In  the  United  States  amebic  dysentery  is  endemic  in  most  of 
the  Southern  States  while  sporadic  cases  have  been  observed 
from  New  England  to  the  Western  Coast. 

Economic  Importance. — It  would  be  hard  to  estimate  the 
economic  importance  of  a  disease  so  prevalent  as  amebic 
dysentery.  According  to  Walker^""'  this  disease,  with  the  pos- 
sible exception  of  malaria,  is  the  most  widespread  of  all  the 
endemic  tropical  diseases.  Walker  quotes  Gauducheau  as 
stating  that  nearly  half  of  the  deaths  of  Europeans  at  Tonkin, 


400  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Indo-China,  are  caused  by  amebic  dysentery  and  Walker  thinks 
where  the  disease  is  not  modified  by  sanitation  about  the  same 
position  of  morbidity  and  mortality  statistics  is  held  by  it  in 
other  tropical  countries. 


CHAPTER  XXVI 
ETIOLOGY  OF  AMEBIC  DYSENTERY 

Season. — There  seems  to  be  some  evidence  that  the  incidence 
of  amebic  dysentery  varies  with  the  season.  Thus,  according 
to  most  observers,  in  the  Philippines  the  disease  is  most  preva- 
lent from  June  to  September.  In  Egypt  it  is  said  to  occur 
most  frequently  in  the  late  summer  and  autumn,  while  in  this 
country  by  far  the  most  cases  are  observed  in  the  warm  months, 
that  is,  from  May  to  September. 

Inundation. — Strong^" ^  states  that  following  the  great  flood 
in  Manila  in  1904  amebic  dysentery  became  almost  epidemic, 
while  Brown '"'^  states  that  numerous  observers  in  Egypt  have 
pointed  out  the  relation  of  the  frequency  of  the  disease  to  the 
annual  overflow  of  the  Nile.  Following  the  overflow  of  the 
Mississippi  River  in  191 2  one  of  us  had  medical  charge  of  3,000 
flood  refuges,  a  large  percentage  of  them  being  accommodated  in 
tents  and  amebic  dysentery  was  very  prevalent. 

Altitude. — Many  observers  have  noted  the  apparant  effect 
of  altitude  on  amebic  dysentery,  it  being  largely  confined  to 
the  low  lying  countries,  along  the  seashore  and  the  valleys  of 
great  rivers  and  rarely  encountered  in  the  uplands. 

Race. — Strong"*"^  states  that  while  the  natives  of  the  Philip- 
pine Islands,  owing  to  their  mode  of  hfe,  are  more  exposed  to 
infection  with  amebic  dysentery  they  are  not  nearly  so  fre- 
quently affected  as  Americans  or  Europeans;  that  while  the 
ratio  of  white  to  native  patients  at  the  Government  Civil 
Hospital  has  been  as  2.5  to  i,  that  of  amebic  dysentery  has 
been  as  9  to  i.  In  direct  contradiction  to  this  statement 
Walker^°°  concludes  that  there  is  no  definite  evidence  of  racial 
immunity  of  the  native  Filipino  to  this  disease.  In  the  South 
there  seems  to  be  no  difference  as  to  susceptibility  between  the 
black  and  white  races,  and  while  amebic  dysentery  is  probably 
more  frequent  in  the  negro  than  the  white  this  is  undoubtedly 
due  to  more  frequent  exposure. 
26  401 


402  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Sex. — That  males  are  much  more  frequently  affected  with 
amebic  dysentery  than  females  is  the  observation  of  all  inves- 
tigators. That  this  is  due  to  the  more  active  life  led  by  the 
former  and  not  to  any  greater  susceptibility  is  also  conceded 
by  all.  According  to  Strong"""^  at  the  Government  Civil 
Hospital  of  401  cases  the  ratio  of  males  to  females  was  4.1 
to  I,  while  of  200  personal  cases  he  states  only  23  were 
females. 

Age. — Musgrave^"'  is  of  the  opinion  that  children  present  a 
partial  natural  immunity  to  infection  with  Amoeba  histolytica. 
He  states  that  not  only  are  children  more  frequently  exposed 
and  less  frequently  infected,  but  when  infection  does  occur  it  is 
usually  less  severe  than  in  adults.  This  investigator  also  con- 
siders that  the  aged  are  also  partially  immune,  but  states  that 
when  attacked  the  aged  are  usually  more  severely  affected. 

DeBuys*"*  does  not  agree  that  children  possess  any  natural 
immunity,  but  considers  the  less  frequent  occurrence  of  the 
disease  in  children  to  be  due  to  their  less  frequent  exposure. 
He  is  of  the  opinion  that  perhaps  owing  to  the  usual  mild 
character  of  the  infection  in  children  it  is  often  overlooked. 

The  youngest  case  observed  by  Musgrave"*"^  was  six  months, 
while  other  observers  have  reported  cases  in  children  as  young 
as  ten  months. 

Occupation. — The  occupation  of  an  individual  seems  to  play 
a  certain  role  in  the  development  of  amebic  dysentery,  those 
whose  occupation  leads  them  into  the  open  being  affected  more 
frequently  than  those  who  remain  within  doors  the  greater 
part  of  the  time.  This  seems  to  be  especially  true  of  field 
laborers. 

j  Other  Predisposing  Causes. — It  would  seem  that  such  factors 
■as  eating  of  indigestible  foods,  chilling  of  the  body,  over-indul- 
gence in  alcohol,  etc.,  may  act  as  predisposing  causes  of  amebic 
dysentery. 

Also  the  existence  of  hemorrhoids,  malaria,  typhoid  fever 
and  other  diseases  may  serve  to  render  the  individual  more 
susceptible  to  infection  with  Amoeba  histolytica. 

Iminimity. — As  stated  above  there  is  some  difference  of 
opinion  as  to  the  relative  immunity  of  children  and  different 


AMEBIC    DYSENTERY  4O3 

races.  We  are  inclined  to  agree  with  Musgrave  that  children 
probably  are  less  susceptible  to  infection,  but  do  not  consider 
that  there  is  any  racial  immunity. 

Epidemics. — While  amebic  dysentery  does  not  occur  in 
widespread  epidemics,  such  as  have  been  known  in  many  other 
infectious  diseases,  numerous  small  epidemics  have  been  ob- 
served in  non-endemic  centers.  Such  an  epidemic  was  reported 
by  Allen'"'^  in  which  a  number  of  persons  were  infected,  sup- 
posedly from  water  from  a  well  used  in  common  with  a  man 
suffering  from  amebic  dysentery. 

Parasite. — Amebic  dysentery  is  now  recognized  to  be  a 
morbid  entity  caused  by  a  specific  microorganism,  the  Endamceba 
histolytica. 

The  biologic  position  of  the  organism  of  amebic  dysentery  is 
of  importance  for  a  thorough  understanding  of  its  life  history 
and  relation  to  disease. 

The  Endamceha  histolytica  is  of  the  protozoa,  a  subkingdom  of 
the  animal  world. 

The  protozoa  are  divided  into  four  orders:  the  Infusoria, 
the  Flagelata,  the  Sporozoa  and  the  Rhizopoda.  It  is  to  the 
latter  order,  which  is  the  lowest  of  the  protozoa,  that  the 
organism  under  discussion  belongs. 

The  Rhizopoda  (ptfa,  root  -|-  tovs  (iro5)  foot)  consists  of 
single  cells  which  move  by  the  extrusion  of  so-called  pseudo- 
podia  or  parts  of  the  cell  substance  and  maintain  their  existence 
by  enclosing  food  in  a  similar  manner.  Of  a  very  extensive 
list  of  suborders  into  which  the  Rhizopoda  are  divided  only 
one,  the  Amceba,  contains  organisms  which  are  parasitic  to 
man. 

The  order  of  Amoeba  is  composed  of  three  genera :  Chlamy- 
dophrys,  Leydenia  and  Amoeba.  Schuadinn  divided  the  genus 
Amceba  into  two  subgenera:  Amceba  and  Endamceba,  and  finally 
as  stated  above,  the  endamceba  into  Endamceba  coli,  a  non- 
pathogenic intestinal  parasite,  and  Endamceba  histolytica  the 
causative  agent  in  amebic  dysentery. 

For  purposes  of  biologic  study  as  well  as  of  diagnosis  it  is 
well  to  compare  Endamceba  histolytica  with  Endamceba  coli. 

Endamceba  Histolytica. — The  average  diameter  of  Endamceba 


404  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

histolytica  in  the  vegetative  stage  is  from  25  to  40  microns,  thus 
averaging  larger  \haiiEndamwha  coli.  Some  specimens  measure 
as  much  as  70  microns  in  diameter.  In  color  the  ectoplasm  is 
glassy,  while  the  endoplasm  is  light  gray,  or  when  blood  is 
present  in  the  feces  it  may  have  a  slight  greenish  tint. 

At  rest  the  organism  is  roughly  spheric  or  oval.  In  locomo- 
tion it  becomes  irregular  or  fantastic,  dependent  upon  the 
extrusion  of  pseudopodia. 

In  young  amebcC  it  may  be  difficult  to  distinguish  the  endo- 
plasm from  the  ectoplasra,  but  in  large  organisms,  especially 
in  motion  the  differentiation  Is  easy.  The  endoplasm  comprises 
about  two-thirds  of  the  protoplasm  and  is  coarsely  granular, 
more  so  than  that  of  E.  coli.  The  ectoplasm  comprising  one- 
third  of  the  protoplasm  is  hyaline  and  lightly  refractive.  In 
fresh  specimens  it  is  frequently  very  difficult  to  distinguish  the 
nucleus.  It  is  situated  to  one  side  of  the  center  of  the  endo- 
plasm. The  average  diameter  is  5  microns.  In  shape  it  is 
circular  or  when  located  at  the  periphery  or  at  the  junction  of 
the  endoplasm  and  ectoplasm  may  be  slightly  flattened.  The 
nucleus  contains  less  chromatin  than  that  of  E.  coli.  The 
great  variations  in  stained  specimens  in  the  appearance  of  the 
nucleus  of  this  parasite  were  largely  responsible  for  the  former 
division  of  the  species  into  E.  histolytica  type  of  nucleus.  The 
nuclear  membrane  is  delicate,  the  chromatin  granules  are  few 
and  lie  upon  the  inner  side  of  the  nuclear  membrane,  the  karyo- 
some  is  very  small  and  appears  as  a  dot  of  chromatin  near  the 
center  of  the  nucleus,  and  there  is  no  centriole.  In  the  so-called 
tetragena  type  of  nucleus  the  nuclear  membrane  is  thicker  and 
better  defined,  the  chromatin  is  more  abundant  and  lies  upon 
the  inner  side  of  the  membrane  or  between  the  membrane  and 
the  karyosome.  The  latter  is  comparatively  large  and  appears 
as  irregular  or  circular  masses  of  chromatin,  and  a  well-marked 
centriole  is  often  present. 

The  endoplasm  always  contains  one  or  more  non-contractile 
vacuoles.  There  may  be  as  many  as  ten  or  more.  When 
numerous  they  vary  in  size  and  are  apt  to  be  small.  When 
single  they  are  frequently  large.  It  is  thought  to  be  dissolved 
hemoglobin  within   the   vacuoles  that  give  the   endoplasm  a 


PLATE    111 


'L^i  '^h 


■mXt^ 


Endamoeba  histolytica,  i.  Living  organisms.  Note  absence  of  nucleus.  All 
three  of  the  parasites  contain  red  blood-corpuscles.  2.  Living  organisms.  Note 
nucleus  in  upper  organism.  The  three  lower  specimens  contain  red  blood-cor- 
puscles.    (Bulletin  No.  i,  Medical  Department,  U.  S.  Army.) 


AMEBIC    DYSENTERY  405 

greenish  tint.  When  the  parasite  is  at  rest  the  vacuoles  are 
spheric  in  shape,  but  in  motion  they  may  become  elongated. 

Endamceha  histolytica  is  much  more  actively  motile  than  in 
Endamceba  coli.  Locomotion  takes  place  by  the  protrusion  of 
pseudopodia.  The  clear  granular  endoplasm  follows,  pouring 
in  until  it  appears  filled.  The  pseudopodia  are  larger  and  more 
distinct  than  in  the  non-pathogenic  parasite.  Motion  without 
locomotion  consists  of  the  extrusion  of  pseudopodia  and  the  ebb 
and  flow  of  endoplasm. 

Endamceba  histolytica  is  actively  phagocytic.  Within  the 
endoplasm  are  engulfed  bacteria,  crystals  and  amorphous 
granules,  and  in  contra-distinction  to  E.  coli  this  parasite 
normally  envelops  red  blood-cells.  As  a  rule  from  two  to  six 
are  present,  but  the  parasite  may  appear  markedly  distended  by 
the  number  of  erythrocytes  which  it  contains. 

In  the  cystic  stage  this  ameba  measures  from  lo  to  20  microns 
in  diameter  and  is  spheric  in  shape.  The  outer  contour  of  the 
organism  is  particularly  distinct  in  stained  specimens  but  in 
fresh  specimens  may  appear  double.  The  chromatin  is  arranged 
in  large  spindle-shaped  masses.  The  cystoplasm  appears  uni- 
form, phagocyted  bodies  having  been  extruded  before  encysta- 
tion  begins.  The  nucleus  elongates,  becomes  constricted  and 
then  divides.  Each  of  these  two  nuclei  then  divides,  forming 
four  daughter  nuclei.  The  four-nucleated  cyst  is  characteristic 
of  E.  histolytica.  In  fully  developed  cysts  the  chromatin  is  not 
infrequently  found  to  have  disappeared. 

In  the  vegetative  stage  the  only  known  method  of  reproduc- 
tion is  by  simple  division.  In  this  process  the  nucleus  elongates, 
becomes  constricted  and  divides,  to  be  followed  by  a  corre- 
sponding process  in  the  cytoplasm,  resulting  in  the  formation  of 
two  organisms. 

Degenerative  forms  of  E.  histolytica  are  not  infrequently 
observed.  They  may  appear  entirely  filled  with  vacuoles,  the 
nucleus  may  appear  almost  entirely  filled  by  the  karyosome, 
or  the  nucleus  may  be  broken  and  scattered  through  the 
cytoplasm. 

The  staining  reactions  for  E.  histolytica  are  similar  to  those 
of  E.  coli. 


4o6  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Endamceba  Coli. — The  limits  of  size  of  Endamtsba  coli  may 
be  put  at  from  6  to  50  microns  in  diameter.  The  average, 
however,  is  from  15  to  25  microns.  While  the  largest 
Endamceba  coli  is  larger  than  the  average  Endamceba  histolytica, 
the  average  size  of  the  former  is  smaller  than  the  average  of 
the  latter.  A  differentiation  should  not  be  made,  therefore, 
upon  size  alone  but,  taken  with  other  morphologic  data,  is 
an  aid. 

At  rest  this  ameba  is  spheric  in  shape.  In  motion  it  varies 
in  form  with  the  protrusion  of  the  pseudopodia. 

The  color  of  Endamceba  coli  is  uniformly  dull  grayish  yellow. 
This  color  is  independent  of  the  composition  of  the  feces, 
whether  bloody  or  otherwise. 

It  is  ordinarily  impossible  to  differentiate  between  the  endo- 
plasm  and  the  ectoplasm  of  E.  coli,  almost  the  entire  pro- 
toplasm being  endoplasm,  and  this  is  a  valuable  point  in  the 
determination  between  the  two  parasitic  species  in  man. 
The  endoplasm  appears  as  finely  granular  in  structure. 

In  E.  coli;  unlike  E.  histolytica,  a  well-defined  nucleus  may 
nearly  always  be  determined.  Its  position  is  usually  to  one  side 
of  the  center.  In  size  it  is  from  5  to  8  microns  in  diameter. 
The  nucleus  is  commonly  spheric,  sometimes  oval,  in  shape  and 
contains  numerous  refractive  granules  and  shreds  of  chromatin 
and  one  or  more  small  nucleoli. 

Vacuoles  are  not  commonly  present  in  this  ameba  and  when 
found  are  single.  In  common  with  the  other  parasitic  species  in 
man  this  vacuole  is  never  contractile.  It  is  usually  indistinct 
and  of  small  size. 

Endamceba  coli  is  only  slightly  motile  as  compared  with 
E.  histolytica.  Motion  in  the  resting  position  may  be  detected 
by  the  flow  of  the  granular  protoplasm  and  the  protrusion  of 
minute  pseudopodia.  Locomotion  is  performed  by  means  of 
small  rounded  pseudopodia.  It  is  very  slow  compared  to  that 
of  E.  histolytica  and  ceases  altogether  after  the  specimen  has 
stood  at  room  temperature  for  half  an  hour. 

This  ameba  frequently  engulfs  bacteria  and  crystals,  but  very 
rarely  red  blood-cells.  Even  when  blood  is  found  in  the 
feces  it  is  rare  to  find  the  corpuscles  phagocyted  by  this  ameba 


AMEBIC    DYSENTERY  407 

and  then  only  one  or  two,  whereas  with  E.  histolytica  several 
corpuscles  are  frquently  found  in  a  single  organism. 

Cysts  of  E.  coli  are  about  a  third  smaller  than  the  vegetative 
forms.  They  possess  a  limiting  wall  of  double  outline  and  are 
motionless.  The  protoplasm  is  hyaline  and  contains  nothing 
but  the  nucleus,  bacteria  and  crystals  having  been  extruded 
before  the  formation  of  the  cyst  wall. 

Reproduction  takes  place  in  the  vegetative  stage  by  two 
methods:  by  simple  division,  resulting  in  two  daughter  amebse; 
and  by  schizogony,  resulting  in  eight  daughter  amebas. 

In  reproduction  by  simple  division  the  nucleus  elongates, 
its  membrane  thins  and  the  chromatin  collects  at  each  pole. 
Next  a  constriction  appears  near  the  center,  narrowing  in  hour- 
glass form  until  complete  separation  occurs  and  two  nuclei  are 
formed.  While  this  is  taking  place  a  corresponding  constriction 
and  division  of  the  protoplasm  occurs  and  two  amebae  are  the 
result.  Schizogonic  reproduction  is  less  common  than  that 
by  simple  division.  In  schizogony  the  nucleus  becomes  swollen 
and  the  quantity  of  its  chromatin  is  greatly  increased.  The 
chromatin  next  collects  in  eight  hemispherical  masses  within 
the  nucleus.  The  nuclear  membrane  then  disappears  and  the 
eight  chromatin  bodies  are  free  in  the  protoplasm  of  the 
ameba.  The  chromatin  masses  become  surrounded  with 
nuclear  membrane,  thus  forming  daughter  nuclei  arranged 
with  more  or  less  regularity  throughout  the  cytoplasm  of  the 
parasite.  The  cytoplasm  then  divides  in  proportion  to  the 
number  of  daughter  nuclei  and  new  organisms  are  formed. 

During  reproduction  within  the  cyst,  the  nucleus  elongates, 
becomes  constricted  and  finally  divides  much  after  the  manner 
described  for  simple  division.  The  further  process  of  autogamy 
is  obscure,  but  after  division  from  two  to  eight  nuclei  are  ob- 
served within  the  cyst,  eight  being  the  normal  number  for  this 
ameba  and  less  than  eight  denoting  that  the  organism  is 
still  in  the  act  of  reproduction.  More  than  eight  nuclei,  some- 
times as  many  as  sixteen,  are  occasionally  observed.  The 
daughter  nuclei  are  spheric  in  shape  and  have  a  distinct  nuclear 
membrane. 

Degeneration    forms    are   sometimes    observed.     These   are 


4o8  ENDEMIC   DISEASES    OF    THE    SOUTHERN    STATES 

characterized  by  poorly  defined  cystic  membranes,  coarse 
granulation  of  the  cytoplasm,  shreds  or  lumps  of  chromatin, 
and  distortion  or  disappearance  of  the  nuclei.  Vacuoles  may 
almost  entirely  replace  the  endoplasm. 

In  the  vegetative  stage  stained  with  hematoxylin  there  is 
no  distinction  between  endoplasm  and  ectoplasm,  while  the 
nucleus  takes  a  dark  purple  color.  With  Wright's  or  Giemsa's 
stain  the  ectoplasm  stains  light  blue  and  appears  structureless, 
while  the  endoplasm  is  darker  blue  and  appears  granular.  On 
account  of  its  chromatin  the  nucleus  takes  a  bright  red  or 
crimson.     The  nucleolus  stains  dark  violet. 

Cultivation  of  Organisms. — Numerous  investigators  have 
attempted  the  artificial  cultivation  of  the  infective  organism 
of  amebic  dysentery,  and  many  reports  of  its  accomplishment 
have  been  published. 

Thus  Musgrave  and  Clegg*"^  considered  that  they  had  been 
successful  in  obtaining  growth  oiAmaha  histolytica  on  a  medium 
of  bouillon  and  agar,  i  per  cent,  alkaline  to  phenolphthalein, 
plus  a  trace  of  peptone.  They  were  unable,  however,  to  ob- 
tain the  organism  in  pure  culture,  but  upon  the  addition  of 
some  bacterial  form,  5.  cholerw  asiatica  being  best  suited,  they 
obtained  good  development  at  room  temperature. 

Lesage^"^  considered  that  he  had  obtained  cultures  of  E. 
histolytica  but  that  E.  coli  could  not  be  grown  artificially. 

Whitmore,""**  Craig'"'^  and  others  after  thoroughly  investigat- 
ing the  matter  have  reached  the  conclusion  that  the  organisms 
which  have  so  far  been  cultivated  are  not  the  parasitic  amebse, 
but  are  free-living  species  which  have  gained  entrance  either 
in  the  cystic  stage  with  the  food  and  passed  through  the 
intestines  or  as  contaminations  of  the  culture  media. 

Inoculation  Experiments. — One  of  the  first  to  attempt  to 
transmit  amebic  dysentery  to  the  lower  animals  was  Loesch.^^^ 
Since  his  time  numerous  investigators  have  performed  inocula- 
tion experiments  on  various  animals  and  in  man,  both  by  feed- 
ing and  by  rectal  injections,  and  in  one  instance'"'"  intra- 
venously, of  feces  containing  amebse  and  of  pus  from  liver 
abscess. 

In  the  classic  experiments  of  Schaudinn^'"  he  fed  kittens  both 


AMEBIC   DYSENTERY  4O9 

with  feces  containing  E.  coli  and  those  containing  E.  histolytica, 
and  showed  conclusively  that  the  former  was  harmless  while  the 
latter  produced  typical  amebic  dysentery.  He  further  showed 
by  an  ingenious  experiment  that  E.  histolytica  is  infectious  only 
when  spores  are  present. 

Craig*^^  found  that  amebic  dysentery  developed  in  50  per 
cent,  of  young  kittens  injected  per  rectum  with  feces  containing 
E.  histolytica,  and  in  65  per  cent,  of  those  fed  with  that  material. 
This  investigator  considers  that  the  negative  results  obtained 
were  due  to  the  feces  containing  the  organisms  only  in  the 
vegetative  state  and  without  spores. 

In  1913  Walker  and  Sellards"^  published  the  results  of  most 
exhaustive  feeding  experiments  on  human  beings.  The  work 
was  carried  on  with  long-term  prisoners  at  the  Bilibid  prison, 
all  of  whom  were  volunteers,  fully  understanding  the  nature 
of  the  experiments  and  having  signed  an  agreement  to  the 
conditions. 

The  experiments  were  most  carefully  controlled  by  previous 
fecal  examinations  for  parasites,  by  controlling  the  food  and 
water  supply,  etc. 

The  first  series  of  experiments  consisted  of  20  feedings  of 
cultures  of  13  strains  and  8  species  of  amebte  to  10  different  men. 
It  was  found  that  the  amebas  could  be  cultivated  from  the 
feces  on  Musgrave  and  Clegg's  medium  for  a  few  days  follow- 
ing the  feeding,  but  never  later.  The  amebas  could  not  be 
recognized  microscopically  by  examination  of  the  feces.  No  dys- 
entery developed.  These  investigators  therefore  concluded 
that  cultivable  amebse  will  not  live  as  parasites  in  the  intestinal 
tract  of  man,  are  not  pathogenic,  and  when  obtained  in  cultures 
from  stools  are  derived  from  cultural  contamination  or  from 
encysted  amebae  which  have  been  ingested  with  water  and  food 
and  passed  unchanged  through  the  intestinal  tract. 

The  second  series  of  experiments  consisted  of  20  feedings  of  5 
strains  of  Endamceba  coli  given  to  20  different  men.  Of  these 
20  men  17  became  parasitized  at  the  first  feeding,  while  3  did 
not.  In  the  17  the  Endamceba  coli  was  found  microscopically 
in  every  case,  while  cultures  on  Musgrave  and  Clegg's  medium 
were  invariably  negative.     None  of  the  men  developed  dys- 


4IO  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

entery.  From  these  experiments  Walker  and  Sellards  con- 
cluded that  the  Endamwba  coli  is  a  strict  parasite,  non-cultivable 
on  Musgrave  and  Clegg's  medium  and  non-pathologic. 

The  third  series  of  experiments  consisted  of  20  feedings  with 
Endamceha  histolytica.  Of  the  20  men  17  became  parasitized 
after  the  first  feeding,  i  after  3  feedings,  while  the  other 
2  were  reserved  as  controls.  Of  the  18  men  who  became 
parasitized  4  developed  endamebic  dysentery.  The  organ- 
isms were  recovered  by  microscopic  examination  in  all  who 
became  parasitized,  but  cultures  on  Musgrave  and  Clegg's 
medium  were  invariably  negative. 

Encysted  "Endamceha  tetragena"  was  obtained  exclusively 
in  the  stools  of  men  who  ingested  Endamceba  histolytica  only. 
Motile  Endamwba  histolytica  were  observed  exclusively  from 
men  who  ingested  "tetragena"  cysts  only.  From  the  above 
experiments  these  authors  conclude  that  Endamceba  histolytica 
is  also  a  strict  parasite  and  cannot  be  cultivated  on  Musgrave 
and  Clegg's  medium;  that  Endamceba  tetragena  and  Endamceba 
histolytica  are  identical;  that  Endamceba histolyticaisthe essential 
etiologic  factor  in  endemic  tropical  dysentery. 

Sellards  and  Baetjer"*^^  in  1914  introduced  the  procedure  of 
direct  inoculation  into  the  cecum  for  the  experimental  produc- 
tion of  amebic  dysentery  in  cats.  Their  method  was  to  perform 
a  laparotomy  under  general  anesthesia  and  inject  the  material 
with  a  sterile  needle  directly  into  the  cecum.  By  this  method 
they  were  able  to  produce  dysentery  in  all  of  ten  animals  with 
the  use  of  eight  strains,  two  of  which  were  from  distinctly 
atypical  cases.  These  authors  consider  that  their  method  of 
inoculation  is  of  value  for  the  propagation  of  a  strain  of  amebas 
through  a  series  of  animals  for  a  period  of  at  least  several  months ; 
that  it  may  be  used  to  determine  the  etiology  of  some  obscure 
diarrheas;  and  that  it  is  of  value  for  the  study  of  the  morphology 
of  some  atypical  amebas  of  low  virulence. 

Mode  of  Infection. — As  the  life  history  of  the  Endamceba 
histolytica  outside  the  human  body  is  unknown,  it  is  rather  diffi- 
cult to  determine  the  source  of  infection.  All  authors  are  agreed 
that  practically  the  only  method  of  infection  in  amebic  dysen- 
tery is  by  the  ingestion  of  the  organisms.     It  is  a  somewhat 


AMEBIC    DYSENTERY  41I 

moot  point,  however,  whether  or  not  drinking  water  is  the  sole 
source  of  infection.  It  is  well  within  the  range  of  possibility 
that  the  infective  organism  may  be  present  on  various  kinds  of 
uncooked  food  such  as  lettuce,  cress,  etc. 

Brown*"^  states  that  a  case  developed  following  the  use  of 
cold  water  enemas  for  constipation.  While  such  cases  are 
obviously  possible  they  must  be  exceedingly  rare. 

Pathogenesis. — The  question  as  to  the  role  of  the  amebae 
found  in  the  intestinal  canal  of  man  in  causing  dysentery  has 
been  a  greatly  mooted  one  and  many  views  have  been  ex- 
pressed. Cassagrandi  and  Barbagallo''^''  considered  that  amebae 
were  not  only  harmless  but  that  they  actually  combated  disease, 
while  Musgrave  and  Clegg'*"^  consider  that  all  amebae  are,  or 
may  become,  pathogenic.  Other  views  are  that  the  amebae 
are  infectious  only  in  the  presence  of  bacteria,  that  they  may 
prepare  the  soil,  as  it  were,  for  the  action  of  certain  bacteria,  or 
vice  versa. 

The  view  is  becoming  more  and  more  prevalent  that  the 
Endamceba  histolytica  is  the  true  and  only  cause  of  the  disease ; 
however,  this  can  be  proven  definitely  only  after  the  successful 
cultivation  of  the  organism  free  from  contamination,  the 
reproduction  of  the  disease  in  animals,  and  the  recovery  in  pure 
culture  of  the  amebae.  Even  the  successful  accomplishment  of 
this  experiment  may  be  open  to  the  objection  that  the  bacteria 
always  found  in  the  intestinal  canal  of  animals  may  in  some 
manner  be  partially  responsible  for  the  production  of  the 
disease. 

This  objection  might  be  overcome  after  the  successful  cul- 
tivation of  the  organism  has  been  accomplished  by  removing 
animals  at  term  by  Cesarean  section,  keeping  them  in  a  sterile  ] 
chamber  supplied  with  sterile  air  and  fed  on  sterile  food  until 
old  enough  for  experimental  purposes,  and  then  injecting  with 
pure  cultures  of  the  organisms. 

It  is  generally  conceded  that  the  usual  portal  of  entry  of 
the  amebae  into  the  tissues  is  by  way  of  the  glands  of  Lieber- 
kiihn.  This  is  shown  to  be  the  case  by  examination  of  the 
intestine  early  in  the  course  of  infection,  when  the  organisms  may 
often  be  found  lying  free  in  the  lumen  of  the  glands  and  the 


412  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

epithelial  lining  remaining  intact.  Later  they  are  found  to 
have  thrust  themselves  between  the  lining  cells  which  to  a  large 
extent  degenerate  as  a  result.  The  orgam'sms  soon  penetrate 
the  basement  membrane  and  spread  out  on  either  side  of  it. 
Here  they  develop  and  push  on  into  the  submucosa  and  feed 
upon  the  tissue  cells,  red  blood-cells  and  perhaps  the  leucocytes. 
In  fresh  tissues  which  are  cut  with  a  warm  knife,  movements  of 
organisms  in  the  tissue  can  be  watched  for  several  hours. 

The  amebae  may  enter  the  radicles  of  the  portal  vein  and  be 
carried  to  the  liver  where  they  may  cause  hepatic  abscess. 


CHAPTER  XXVn 
PATHOLOGY  OF  AMEBIC  DYSENTERY 

The  morbid  anatomy  of  amebic  dysentery  is  confined  mainly 
to  the  large  intestine,  the  sigmoid  and  rectum,  though  oc- 
casionally the  lower  end  of  the  ileum  may  be  involved  by 
extension  through  the  ileocecal  valve,  and  the  appendix  has 
been  found  affected.  There  are  also  certain  complications 
which  may  arise,  causing  pathologic  processes  in  other  loca- 
tions than  the  bowels. 

The  pathologic  anatomy  as  observed  in  the  large  intestine 
in  amebic  dysentery  presents  many  features  which  are  charac- 
teristic of  this  disease.  This  is  especially  true  of  the  chronic 
protracted  cases,  but  as  may  readily  be  imagined  the  condition 
will  depend  largely  upon  the  severity  of  the  infection,  and  in 
very  acute  cases  when  death  results  early,  the  lesions  may  not 
present  typical  findings. 

In  the  latter  type  of  cases  the  colon  shows  evidence  of  marked 
inflammation,  the  mucous  membrane  being  hyperemic  and 
inflamed  with  but  little  change  in  the  submucosa.  It  is 
swollen,  of  a  dark  bluish  or  purple  color,  and  presents  many 
extravasations  from  congested  vessels.  Ulceration  is  infrequent, 
though  small  superficial  areas  of  necrosis  are  noted.  Diphther- 
itic-appearing membranes  are  often  seen,  composed  of  the  ex- 
cessive mucous  secretion  and  portions  of  the  mucosa  which 
have  separated  from  the  intestinal  wall.  The  whole  picture 
presents  a  marked  resemblance  to  that  observed  in  acute  bacil- 
lary  dysentery. 

This,  however,  is  not  the  case  in  the  more  chronic  type  of 
amebic  dysentery.  In  such  cases  of  moderate  severity  the 
peritoneum  is  found  more  or  less  injected,  contains  some  fluid, 
but  otherwise  presents  little  that  is  abnormal.  The  large 
intestine  is  bright  in  color,  smooth  and  shows  patches  of  con- 
gestion. The  mucosa  is  seen  to  possess  an  excess  of  secretion 
413 


414  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

and  presents  some  points  of  hyperemia  and  ecchymosis.  The 
enamebce  usually  first  enter  the  crypts  of  Lieberkiihn  and 
penetrate  the  epithelial  lining  by  boring  between  the  cells 
with  their  pseudopodia  and  after  passing  through  the  base- 
ment membrane  enter  the  submucosa.  Here  they  multiply 
rapidly  and  are  reinforced  by  others  from  the  lumen  of  the 
intestine.  By  their  presence  in  the  submucosa,  areas  of 
congestion  are  formed;  the  mucosa  is  covered  by  a  more  or  less 
copious  secretion  of  viscid  mucus  and  in  severe  cases  with  a 
diphtheroid  membrane.  It  is,  however,  in  the  submucosa 
that  the  principal  changes  take  place.  There  are  evidences  of 
acute  inflammation  and  proliferation  of  the  fibers  of  the  con- 
nective tissue.  Small  tumors  of  adenoid  tissue  are  formed  which 
may  be  seen  on  the  surface  of  the  mucosa.  Later  these  sup- 
purate in  the  center  and  present  one  of  the  characteristic  lesions 
of  the  disease.  In  the  early  stage,  also,  are  seen  small  erosions 
and  areas  of  necrosis.  They  are  in  the  beginning  superficial 
and  separate,  but  they  gradually  extend,  deepen  and  are  joined 
together  and  cover  rather  large  areas  of  the  surface.  These 
erosions  later  constitute  the  typical  ulcers  of  the  disease.  Be- 
tween them  the  mucosa  appears  normal  except  for  the  congested 
vessels. 

Two  types  of  ulceration  are  seen:  First,  the  typical  under- 
mined amebic  ulcers  which  in  the  early  stages,  as  has  been 
pointed  out,  are  seen  as  small  erosions  on  the  mucosa.  As  the 
process  continues,  a  pocket  is  formed  in  the  submucosa  which 
is  extended  in  all  directions  parallel  with  the  surface.  The 
base  of  the  ulcer  rests  upon  the  circular  muscular  coat  with 
overhanging  edges  of  mucosa.  The  size  of  the  ulcer  varies 
from  I  mm.  in  diameter  to  8  or  lo  cm.  As  may  be  expected, 
the  submucosa  becomes  markedly  thickened  and  edematous, 
and  usually  the  muscular  and  serous  coats  are  somewhat  in- 
volved in  a  like  manner.  It  is  not  unusual  in  severe  cases 
for  two  or  more  ulcers  to  coalesce  either  in  the  submucosa 
alone,  forming  tunnels  under  the  mucosa,  or  by  sloughing 
away  of  the  mucosa  itself.  In  very  severe  cases  the  muscular 
coat  may  be  involved,  necrosis  or  even  perforation  taking 
place     and     the     peritoneum     or     omentum     forming     the 


AMEBIC    DYSENTERY  415 

base  of  the  ulcer.  The  ulcer  may  perforate  into  the  subperi- 
toneum  where  it  may  remain  circumscribed,  may  burrow 
widely,  or  may  cause  general  peritonitis. 

The  second  type  of  ulcer  seen  in  amebic  dysentery  is  the  so- 
called  type  of  Harris.  These  ulcers  are  rarer  than  the  typical 
or  undermined  ulcer  but  are  not  infrequently  seen,  especially 
in  early  and  rather  acute  cases.  The  Harris  ulcers  are  in  the 
beginning  confined  mainly  to  the  mucosa,  and  for  this  reason 
there  is  some  doubt  as  to  their  exact  connection  with  amebic 
dysentery.  They  may  extend  into  the  submucosa,  but  rarely 
penetrate  it  and  never  extend  into  the  muscular  coat.  The 
edges  of  the  ulcer  are  abrupt,  thickened  and  congested.  They 
are  sometimes  described  as  of  punched-out  appearance.  The 
base  of  the  ulcer  is  clean,  edematous  and  of  a  grayish  color. 

Histopathology. — The  mucosa  between  the  ulcers  generally 
presents  little  abnormality  upon  microscopic  examination. 
Near  the  ulcers  the  mucosa  may  be  hypertrophied,  with  some 
mucoid  degeneration  and  occasionally  cyst  formation.  Often 
the  cells  lining  the  glands  are  seen  to  have  separated  from  the 
basement  membrane  and  amebae  may  be  found  among  these 
cells. 

In  the  beginning  the  most  noticeable  condition  is  a  marked 
congestion,  and  often  capillary  hemorrhages  are  seen  beneath 
the  mucosa.  The  submucosa  may  also  show  congestion  with 
thickening  due  to  edema.  There  is  an  infiltration  of  lymphoid 
cells  into  the  interglandular  tissue. 

Later  in  the  disease  a  slight  superficial  necrosis  is  seen  and 
the  glands  surrounding  the  lesions  show  hypertrophy  and 
mucoid  degeneration.  There  is  more  infiltration  and  more 
congestion.  Within  the  interglandular  connective  tissue 
amebae  are  seen  in  the  blood-vessels  and  lymph  spaces.  As 
the  process  advances  the  submucosa  is  seen  to  be  more  affected. 
Congestion  and  edema  are  more  pronounced  and  amebae  are 
seen  to  be  more  plentiful.  Sometimes  there  is  an  infiltration 
of  polymorphonuclear  leucocytes  which  seems  to  be  accom- 
panied by  activity  of  bacteria.  The  ulcer  contents  in  uncom- 
plicated cases  are  composed  of  a  granular  base  with  degenerated 
cells,  amebae,  bacteria  and  erythrocytes. 


4l6  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Amebic  ulcers  show  a  marked  tendency  to  heal.  After  the 
necrotic  area  has  sloughed,  red  granulations  are  seen  in  the  base 
of  the  ulcer.  These  granulations  are  unstable-and  break  down 
easily,  and  as  long  as  amebtC  are  present  no  permanent  repair 
takes  place.  In  small  ulcers  complete  repair  may  occur,  but 
in  large  ones  scar  tissue  is  formed  followed  by  more  or  less 
marked  contraction. 

Complications. — The  most  important  complication  of  amebic 
dysentery  is  hepatic  abscess.  According  to  Brown*"-  there  are 
four  routes  by  which  the  amebae  may  gain  access  to  the  liver 
as  follows :  (i)  Directly  from  the  lumen  of  the  intestinal  canal; 
(2)  transperitoneally  from  the  intestinal  wall;  (3)  by  the  portal 
vessels;  (4)  by  the  general  circulation. 

Infection  of  the  liver  by  way  of  the  portal  circulation  is  by 
far  the  most  frequent  route. 

According  to  Craig"^  Roux  in  639  collected  cases  of  hepatic 
abscess  found  the  location  to  be  as  follows:  435,  or  70.8  per 
cent.,  in  the  right  lobe;  85,  or  13.3  per  cent.,  in  the  left  lobe; 
and  2,  or  0.3  per  cent.,  in  the  lobus  Spigelli. 

It  was  formerly  considered  that  hepatic  abscess  of  amebic 
origin  are  usually  single  but  of  recent  years  it  has  been 
shown  that  this  is  usually  not  the  rule  and  that  multiple 
abscesses  are  observed  at  least  as  frequently  as  in  50  per  cent, 
of  cases. 

The  size  of  liver  abscesses  varies  greatly.  They  may  be  so 
small  as  to  be  microscopic  or  they  may  attain  a  size  so  large 
as  to  fill  almost  completely  the  abdomen. 

The  first  change  noted  in  beginning  hepatic  abscess  is  the 
formation  of  one  or  more  small  irregularly  spheric  nodules  which 
appear  like  commencing  coagulation  necrosis  and  to  some 
degree  resemble  the  lesions  observed  in  the  intestinal  tract. 
The  nodules  are  solid  and  upon  being  cut  appear  of  a  cheesy 
consistency,  the  lobular  markings  being  obliterated.  Later  the 
patches  may  coalesce  and  begin  the  breakdown.  The  process 
may  be  stopped  at  this  point  and  occasionally  found  as  de- 
scribed. As  a  rule  the  breaking  down  continues  and  liquefac- 
tion takes  place,  followed  by  the  formation  of  a  cavity  which  is 
filled  with  viscous  fluid.     This  fluid  is  usually  dark  red  in  color 


AMEBIC    DYSENTERY  417 

and  of  gelatinous  consistence.  It  may,  however,  be  of  a  green- 
ish color  owing  to  the  mixture  with  bile.  As  the  process  ad- 
vances the  contents  become  more  liquid  and  necrotic  tissue  may 
be  found  floating  in  the  mass.  There  is  usually  no  lining  mem- 
brane of  the  cavity  especially  when  of  large  size  but  occasionally 
the  small  abscesses  may  have  clearly  defined  smooth  walls.  It 
may  be  that  the  vascular  structures  are  not  destroyed  and  are 
seen  crossing  the  cavity.  Microscopically  the  contents  of  liver 
abscess  are  seen  to  be  made  up  of  disorganized  liver  cells,  red 
blood  corpuscles  and  granular  matter.  Fat  globules,  choles- 
terin,  Charcot-Leyden  crystals  and  hemotoidin  are  recognized. 
Pus  cells  are  usually  not  present.  The  amebs  are  found  if  the 
abscess  is  not  old.  They  are,  however,  found  in  the  walls  of 
practically  all  abscesses.  The  liver  cells  show  hyaline  and 
granular  destruction.  If  the  abscess  is  contaminated  by  pyo- 
genic bacteria  the  tissues  will  show  many  leucocytes. 

Other  complications  of  the  liver  that  are  frequently  noted  are 
fatty  degeneration  and  cirrhosis. 

The  spleen  is  frequently  the  seat  of  cirrhosis;  infarcts  are 
occasionally  seen,  while  splenic  abscess  has  been  reported. 
The  route  of  infection  is  probably  usually  the  blood  stream 
although  the  infection  may  extend  from  the  splenic  flexure  of 
the  colon. 

Chronic  gastritis  is  not  a  rare  complication  of  amebic  dys- 
entery and  is  usually  of  a  rather  severe  character. 

Chronic  enteritis  is  often  seen,  while,  as  pointed  out  above, 
acute  peritonitis  may  occur  and  amebic  appendicitis  is  not 
uncommon. 

The  kidneys  are  very  often  the  seat  of  nephritis,  usually  of 
a  chronic  character. 

In  the  heart,  valvular  disease  is  rarely  seen,  while  edema  of  the 
pericardium  is  occasionally  observed.  Arteriosclerosis  is  some- 
times found. 

The  lungs  are  quite  frequently  found  to  be  the  seat  of  bron- 
chopneumonia. This  is  in  all  probability  mainly  due  to  the 
fact  that  the  patient  remains  in  a  recumbent  position  for  so 
long  a  time.  This  complication  is  almost  always  fatal.  Lobar 
pneumonia  is  occasionally  seen  and  usually  ends  with  death. 
27 


41 8  ENDEMIC   DISEASES    OF    THE    SOUTHERN    STATES 

Empyema  may  occur,  due  to  the  perforation  into  the  pleural 
cavity  from  an  hepatic  abscess. 

Brain  abscess  is  a  rather  rare  compHcation  of  amebic  dys- 
entery and  usually  follows  hepatic  abscess.  The  abscesses  are 
usually  small  and  may  even  be  microscopic  in  size.  The  amebae 
are  readily  demonstrable  in  the  pus  and  the  walls  of  the  cavity, 
and  bacteria  of  various  kinds  are  usually  present. 


CHAPTER  XXVIII 
CLINICAL  HISTORY  OF  AMEBIC  DYSENTERY 

The  clinical  course  of  amebic  dysentery  varies  greatly.  It 
may  be  ushered  in  with  a  chill,  nausea  and  vomiting,  and 
pass  on  with  acute  griping  pain  and  diarrhea  followed  by  pros- 
tration, exhaustion,  collapse,  cardiac  failure  and  death.  Or 
after  such  an  acute  attack  either  with  or  without  treatment  the 
system  may  overcome  the  infection  and  after  four  or  five  days 
improvement  begin.  Complete  recovery  is  rather  rare  and  a 
tendency  to  relapse  and  chronicity  may  continue. 

On  the  other  hand,  the  onset  of  the  disease  may  be  insidious 
and  persist  for  years  with  only  mild  disturbances,  such  as  ir- 
regularity of  the  bowels,  occasional  abdominal  discomfort,  and 
gastric  derangement.  This  type  of  the  disease  may  develop 
acute  symptoms  at  any  time  and  terminate  in  death  or 
recovery. 

The  period  of  time  elapsing  from  the  ingestion  of  E.  histolytica 
until  they  could  be  found  in  the  stools  microscopically  in  the 
experimental  cases  of  Walker  and  Sellards*^^  varied  from  one 
to  forty-four  days  with  an  average  of  nine  days.  Of  the  four 
cases  which  developed  dysentery  the  incubation  periods  until 
the  advent  of  symptoms  were  respectively,  twenty,  fifty-seven, 
eighty-seven  and  ninety-five  days.  These  authors  consider 
that  it  is  at  least  probable  that  the  number  of  organisms  in- 
gested accounts  for  the  varying  incubation  periods. 

In  the  experiments  of  Sellards  and  Baetjer*'^  on  cats  the 
incubation  period  of  animals  injected  from  acute  and  chfonic 
amebic  dysentery  varied  from  six  to  ten  days,  while  in  the 
animals  injected  with  atypical  strains  the  incubation  period 
was  one  month. 

In  the  acute  form  of  the  disease  there  may  be  some  prodromal 
symptoms  such  as  malaise  and  headache.  After  three  to  five 
419 


420  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

days  marked  nausea,  which  vomiting  does  not  altogether  re- 
lieve, is  usually  noted.  A  distinct  rigor  may  be  the  first  marked 
symptom  or  the  nausea  and  vomiting  may  be  accompanied 
by  chilly  sensations.  In  a  short  time  diarrhea  with  severe  grip- 
ing pain  develops.  The  pain  is  at  first  of  an  intermittent  acute 
character  most  marked  in  the  umbilical  regions;  later  this  is 
less  acute  but  continuous  and  is  located  in  the  region  of  the 
sigmoid. 

At  first  the  stools  are  copious  and  watery  but  later  are  scanty 
and  composed  mainly  of  mucus,  blood  and  cast-off  fragments 
of  intestinal  epithelium.  The  movements  become  more  fre- 
quent, sometimes  as  many  as  fifty  a  day,  and  urgent,  and  are 
attended  with  burning  and  tenesmus.  Following  defecation 
there  is  no  relief  and  even  though  the  rectum  be  almost  entirely 
empty  the  desire  to  defecate  remains  and  violent  efforts  are  made 
to  do  so.  Not  only  is  rectal  tenesmus  present  but  very  fre- 
quently vesical  tenesmus  is  one  of  the  most  distressing  symp- 
toms. In  the  malignant  cases  there  is  a  continued  increase  in 
the  severity  of  the  symptoms.  The  pain  and  loss  of  sleep 
often  cause  mental  symptoms,  either  depressions  or  delirium, 
to  develop.  There  may  be  severe  hemorrhages  of  the  bowels. 
Exhaustion  soon  appears  and  in  a  few  hours  death  results  from 
cardiac  failure  and  collapse. 

If  the  system  is  able  to  throw  off  the  infection,  or  sometimes 
under  proper  treatment  the  acute  stage  is  followed  in  four  or 
five  days  by  beginning  recovery.  The  pain  becomes  less,  the 
bowel  movements  less  frequent,  but  contain  more  fecal  matter. 
Complete  recovery  is  unusual  and  the  disease  passes  into  either 
the  chronic  or  the  intermittent  form.  In  the  former  the  stools 
vary  from  2  or  3  to  lo  or  15  per  day  with  more  or  less  pain.  As 
the  disease  progresses  there  is  loss  of  weight,  anorexia,  indiges- 
tion and  flatulence.  Extreme  emaciation  may  result  with 
great  exhaustion.  Death  may  follow  from  exhaustion  or  inter- 
current infection.  In  the  intermittent  type  there  are  periods 
of  diarrhea,  more  marked  in  the  mornings,  consisting  of  two 
to  four  semifluid  stools  without  much  mucus  and  little  pain. 
The  diarrhea  lasts  for  one  to  six  or  eight  days  and  is  followed  by 
a.  period  of  constipation.     These  alternate  periods  of  diarrhea 


AMEBIC    DYSENTERY  42 1 

and  constipation  may  last  for  many  years  and  the  patient  die 
of  intercurrent  disease  or  an  acute  exacerbation  may  lead 
to  a  fatal  outcome. 

That  mild  cases  of  infection  with  Endamosba  histolytica,  in 
which  there  are  no  dysenteric  symptoms,  do  occur  has  been 
pointed  out  by  many  observers.  Thus  Musgrave*^^  reports  a 
series  of  fifty  cases  in  which  characteristic  amebic  lesions  were 
present  at  autopsy  but  in  which  dysentery  symptoms  were 
absent.  Such  symptoms  as  abdominal  "aching,"  more  pro- 
nounced at  night  and  early  in  the  morning,  flatulence  and 
constipation  are  noted.  The  constipation  is  usually  resistant 
to  the  ordinary  doses  of  the  usual  cathartics,  or  their  actions 
may  be  unusually  severe  and  prolonged.  Loss  of  weight  is 
often  noticed  but  this  may  not  result,  and  the  patient  may  even 
gain  in  iiesh.  Anorexia  is  often  first  noticed  at  breakfast 
time  and  is  frequently  accompanied  by  nausea  and  accumula- 
tion of  mucus  in  the  mouth  and  throat  during  the  night.  One 
of  the  most  frequently  noted  S3anptoms  is  excessive  perspira- 
tion, especially  of  the  palms  of  the  hands  and  the  soles  of  the 
feet.  Often,  as  Musgrave  points  out,  the  whole  chain  of  symp- 
toms, dullness,  headache,  loss  of  memory,  weakness,  desire  for 
sleep,  etc.,  is  noted  in  these  mild  infections.  The  disease  often 
begins  insidiously  and  passes  into  a  slightly  more  accentuated 
form  which  may  persist  for  months  or  years.  This  type  of 
infection  is  similar  to  the  chronic  type  following  an  acute  out- 
break and  may  develop  at  any  time  an  acute  attack. 

Physical  Signs. — By  physical  examination  in  amebic  dysen- 
tery little  or  nothing  distinctive  may  be  learned.  During 
acute  attacks  there  is  more  or  less  tenderness  over  the  large 
intestine,  especially  over  the  sigmoid.  The  liver  is  usually 
enlarged  and  in  some  cases  of  hepatic  abscess  enormously  so. 
At  first  the  abdomen  is  more  or  less  distended  with  gas  but  later 
is  flat  and  the  abdominal  muscles  are  flaccid. 

Temperature. — The  temperature  in  amebic  dysentery  varies 
from  normal  or  subnormal  in  the  mild  cases  to  104°  to  io5°F. 
in  the  severe  attacks  of  acute  onset.  Just  before  death  in  the 
acute  cases  the  temperature  may  drop  to  subnormal.  In  un- 
complicated cases  even  of  moderate  severity  there  is  usually 


42  2  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

no  rise  in  temperature,  but  in  cases  of  secondary  infection  the 
temperature  may  be  high.  In  the  acute  attacks,  which  occur 
during  the  course  of  a  chronic  case,  even  if  of  marked  severity, 
the  temperature  is  usually  not  so  high  as  in  the  attacks  of  acute 
onset. 

Ptilse  and  Respiration. — The  pulse  and  respiration  as  a  rule 
follow  the  variation  in  temperature.  In  the  mild  cases  and 
those  of  chronic  character  the  pulse  may  be  normal,  while  in 
moderately  severe  cases  the  pulse  changes  from  80  to  100. 
In  the  acute  cases  the  pulse  rate  may  run  as  high  as  no  to 
120,  and  in  those  of  fatal  termination  120  to  140  and  more  have 
been  noted.  The  respirations  as  a  rule  increase  with  the  pulse, 
except  as  collapse  occurs  in  which  they  are  shallow  and  in- 
frequent. The  blood  pressure  in  amebic  dysentery  depends 
upon  the  general  condition  of  the  patient;  where  there  is 
emaciation  and  cachexia  the  blood  pressure  is  low,  while  in 
mild  and  even  in  some  chronic  cases  it  may  be  normal.  In 
cases  complicated  by  other  conditions  such  as  nephritis  and 
arteriosclerosis  the  blood  pressure  may  be  high.  As  a  rule  there 
are  no  symptoms  referable  to  the  heart,  though  pathologic 
changes  in  this  organ  may  occur. 

The  blood  stream  in  amebic  dysentery  shows  nothing  which 
is  typical.  In  those  cases  of  acute  onset  there  is  nothing  ab- 
normal seen,  the  erythrocytes  show  no  alterations  in  shape  or 
numbers,  and  the  hemoglobin  is  of  normal  percentage.  There 
may  be  a  slight  leucocytosis. 

In  the  more  chronic  cases  there  is  a  secondary  anemia  de- 
pending in  degree  upon  the  severity  and  length  of  the  infection. 
The  red  blood-cells  are  decreased  in  numbers  to  as  low  as  1,500,- 
000  or  less,  while  poikilocytes,  normoblasts  and  megaloblasts 
may  be  found.  The  hemoglobin  is  diminished  in  amount  in  a 
proportion  greater  than  the  reduction  of  the  erythrocytes.  It 
may  be  as  low  as  20  to  30  per  cent.  There  is  usually  a  moderate 
leucocytosis  in  the  later  stages  of  the  disease  depending  to  a 
large  extent  upon  the  amount  of  secondary  infection.  The 
relative  numbers  of  the  various  types  of  leucocytes  are  usually 
normal.  There  is  rarely  an  eosinophilia  in  cases  uncom- 
plicated by  other  intestinal  parasites,  although  as  pointed  out 


AMEBIC    DYSENTERY  423 

by  Amberg''^^  in  children  this  condition  is  very  frequently 
encountered. 

All  symptoms  observed  which  are  referable  to  the  lungs 
occur  as  complications. 

The  gastro-intestinal  symptoms  are  most  marked  in  amebic 
dysentery.  Thus  nausea  and  vomiting  are  early  symptoms 
in  acute  attacks,  and  as  pointed  out  above  in  those  mild  in- 
fections without  dysenteric  symptoms  the  only  symptoms  may 
be  those  referable  to  the  stomach.  The  appetite  varies  with 
the  severity  of  the  condition.  In  mild  and  chronic  cases  it 
may  be  normal  while  in  the  more  severe  cases  there  may  be 
complete  anorexia. 

As  pointed  out  above,  the  intestinal  symptoms  may  vary  all 
the  way  from  constipation  to  the  most  marked  diarrhea  of 
the  dysenteric  type.  It  is  not  at  all  to  be  inferred  that  the 
pathologic  findings  are  to  be  interpreted  in  the  light  of  the 
clinical  evidence  for  it  not  infrequently  occurs  that  cases  show- 
ing marked  dysenteric  lesions  come  to  autopsy  without  having 
shown  dysenteric  symptoms. 

Macroscopically  the  stools  of  amebic  dysentery  show  nothing 
characteristic  of  this  disease.  They  vary  in  consistence  from 
solid  and  semi-solid  in  the  mild  and  chronic  conditions  to  watery 
in  the  acute.  When  formed  stools  are  passed  there  may  or 
may  not  be  a  coating  of  mucus.  The  fluid  stools  show  the  most 
marked  variations.  There  may  be  little  present  but  blood, 
mucus  and  intestinal  debris,  or  there  may  be  noted  particles  of 
undigested  food.  Again  they  often  assume  a  watery  consistence 
with  little  mucus.  When  ulceration  is  present  the  stools  may 
contain  blood  clots  and  portions  of  intestinal  mucosa.  The 
odor  of  the  amebic  feces  is  usually  very  offensive  and  accord- 
ing to  Musgrave''"  "all  but  characteristic."  This  author 
further  states  that  the  odor  is  so  nearly  characteristic  that 
diagnostic  importance  may  be  attached  to  it. 

The  nature  of  the  blood  as  passed  in  the  feces  is  of  importance 
both  as  an  indication  of  the  severity  of  the  pathologic  process 
and  the  location  of  the  lesions.  If  no  blood  is  present  macro- 
scopically, it  is  an  indication  that  ulceration  probably  has  not 
taken  place.     This  is  not  invariable  as  in  very  acute  cases 


424  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

perforation  may  take  place  before  ulceration.  If  the  blood  is 
of  dark  brown  or  black  color,  it  is  an  indication  that  the  cecum 
is  the  chief  seat  of  the  infection.  If  the  blood  is  fresh,  bright 
red  and  clotted,  it  may  be  assumed  that  the  lower  end  of  the 
colon  is  most  affected,  while  if  the  blood  is  intimately  mixed 
with  mucus  and  fecal  matter  and  the  stools  are  of  a  dark  red  or 
reddish-brown  color,  it  is  probable  that  the  bleeding  is  taking 
place  above  the  sigmoid  flexure. 

Microscopically  the  appearance  of  the  feces  in  amebic  dysen- 
tery varies  with  the  stage  of  the  disease  and  the  severity  of  the 
infection.  Red  blood-cells  are  practically  always  found  and 
more  or  less  epithelium.  There  are  varying  quantities  of  food 
particles,  epithelioid  and  pus  cells,  bacteria  and  the  distinguish- 
ing feature,  Endamceba  histolytica.  It  must  be  remembered 
that  Endamceba  coli  are  also  frequently  present  as  well  as  the 
ova  of  certain  other  intestinal  parasites; 

The  urine  in  amebic  dysentery  shows  nothing  characteristic. 
The  amount  is  usually  greatly  diminished  during  the  acute 
attacks,  but  may  be  normal  during  the  intervening  periods. 
The  specific  gravity  corresponds  to  the  amount  secreted  and 
the  reaction  is  usually  acid.  Retention  may  occur  in  the  severe 
cases  when  the  reaction  may  become  alkaline.  Albuminuria  is 
seen  only  when  the  disease  is  complicated  by  nephritis.  Al- 
bumoses  have  been  noted  and  may  be  indicative  of  hepatic 
abscess.  Indican  is  usually  present  in  considerable  quantity, 
depending  on  the  severity  of  the  pathologic  processes.  It  has 
been  noted  that  the  chlorides  are  diminished  or  absent  during 
acute  attacks,  especially  when  the  diarrhea  is  severe  and  the 
stools  watery.  Microscopically  may  be  found  hyaline  and 
granular  casts,  if  nephritis  is  present,  and  epithelial  cells  and 
various  crystals. 

Complications. — As  stated  in  the  chapter  on  pathology  the 
most  important  complication  of  amebic  dysentery  is  hepatic 
abscess.  This  may  occur  early  in  the  disease  but  is  usually  a 
later  complication. 

Cases  have  been  reported  in  which  liver  abscess  preceded 
other  manifestations  of  amebic  infection  but  this  is  undoubtedly 
rare.     In  cases  of  acute  onset  hepatic  abscess  may  be  found 


AMEBIC    DYSENTERY  425 

within  a  week  of  the  onset  of  dysenteric  symptoms,  but  as  a 
rule  is  not  noted  till  about  the  sixth  week.  In  chronic  cases, 
however,  this  complication  may  not  develop  for  months  or 
even  years  after  the  initial  attacks.  In  one  case  reported 
by  Brown''"^  the  patient  developed  hepatic  abscess  nine  years 
after  the  last  attack  of  dysentery. 

According  to  Manson*^^  Europeans  are  more  liable  to  develop 
hepatic  abscess  than  natives  of  tropical  countries  (India) 
although  more  dysentery  is  seen  in  the  natives.  He  further 
states  that  while  European  women  contract  amebic  dysentery 
as  frequently  as  European  men  they  rarely  develop  hepatic 
abscess  and  children  hardly  ever.  One  of  us  has  operated  on 
half  a  dozen  cases  of  amebic  abscess  in  adult  negroes,  all  but 
one  being  males.  The  onset  is  usually  insidious  and  may  last 
for  a  considerable  length  of  time  without  any  symptoms.  Symp- 
toms of  perforation  may  be  the  first  indication.  Pain  usually 
develops  some  time  in  the  course  of  the  disease  and  is  usually 
dull  and  aching  but  may  be  sharp.  The  pain  may  be  over  the 
hypochondrium  or  epigastrium,  or,  as  is  very  frequently  the 
case,  it  may  be  reflex  and  observed  in  the  region  of  the  right 
scapula.  If  pain  is  absent,  it  may  sometimes  be  elicited  by 
pressure  over  the  liver.  A  rise  in  temperature  is  usual  but  not 
constant.  The  morning  temperature  may  be  nearly  normal  and 
in  the  evening  a  rise  to  ioo°  to  ioi°F.  be  noted.  On  the  other 
hand,  a  temperature  of  103°  to  io4°F.  is  not  infrequent.  The 
temperature  is  usually  intermittent  but  it  may  be  continuous 
for  a  long  time  with  slight  morning  remissions.  Chills  and 
excessive  perspiration  may  occur.  The  pulse  usually  corre- 
sponds to  the  temperature  and  may  run  as  high  as  140  or  more. 

Marked  jaundice  is  rare,  although  the  conjunctivae  are  fre- 
quently tinged  with  yellow.  Vomiting  is  not  usual  and  anorexia 
is  the  rule.     The  tongue  is  usually  coated. 

Physical  examination  will  reveal  an  enlarged  liver  and  if  the 
abscess  is  located  anteriorly  and  of  very  large  size  fluctuation 
may  be  noted.  If  it  is  located  under  the  vault  of  the  diaphragm, 
there  will  be  bulging  upward  and  an  area  of  dullness  will  be 
noted  in  the  thorax.  The  intercostal  spaces  may  be  obliterated 
and  protrude. 


426  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

The  blood  in  hepatic  abscess  usually  shows  a  leucocytosis, 
although  this  condition  is  by  no  means  constant.  The  total 
number  of  leucocytes  may  run  as  high  as  30,000  or  40,000  mainly 
due  to  an  increase  in  the  polymorphonuclears. 

If  the  patient  is  not  operated  upon  and  lives  long  enough, 
spontaneous  rupture  may  occur.  This  most  frequently  is 
into  the  right  lung,  less  often  into  the  peritoneum  and  pleural 
sac,  and  rarely  into  the  colon,  the  stomach,  small  intestine, 
bile  ducts,  vena  cava,  pericardium,  kidney,  or  through  the 
skin  in  the  lumbar  or  right  hypochondriac  region. 

Manson*^^  gives  the  following  table  of  563  cases  of  hepatic 
abscess  collected  by  Rendu  in  which  rupture  occurred  in  159: 

Rupture  occurred  into  the  pericardium  in  i  case,  0.13  per  cent. 

Rupture  occurred  into  the  pleura  in  31  cases,  5.5  per  cent. 

Rupture  occurred  into  the  lung  in  59  cases,  10,5  per  cent. 

Rupture  occurred  into  the  peritoneum  in  39  cases,  6.9  per  cent. 

Rupture  occurred  into  the  colon  in  6  cases,  i  per  cent. 

Rupture  occurred  into  the  stomach  and  duodenum  in  8  cases,  1.4  per  cent. 

Rupture  occurred  into  the  bile  duct  in  4  cases,  0.7  per  cent. 

Rupture  occurred  into  the  vena  cava  in  3  cases,  0.5  per  cent. 

Rupture  occurred  into  the  kidney  in  2  cases,  0.3  per  cent. 

Rupture  occurred  into  the  lumbo-iliac  region  in  6  cases,  i  per  cent. 

One  of  us  has  recently  treated  a  case  in  which  rupture  of  an 
abscess  occurred  into  the  right  lung.  Ten  months  later, 
though  pus  was  being  expectorated  freely,  the  abscess  pointed 
just  to  the  right  of  the  second  lumbar  vertebra  where  it  was 
evacuated  through  an  incision. 

Peritonitis  may  occur  as  a  result  of  rupture  of  an  hepatic 
abscess  into  the  peritoneum  or  following  perforation  of  the 
intestine.     This  condition  usually  proves  fatal. 

Other  Diseases. — Amebic  dysentery  is  very  frequently  com- 
plicated by  other  diseases,  such  as  malaria,  pellagra,  hook-worm 
and  other  intestinal  parasites,  which  complications  will  cause 
variations  in  the  symptomatology.  We  have  seen  pyorrhoea 
alveolaris  complicating  amebic  abscess  of  the  liver. 


CHAPTER  XXIX 
DIAGNOSIS  OF  AMEBIC  DYSENTERY 

The  absolute  diagnosis  of  amebic  dysentery  upon  clinical 
findings  alone  is  usually  impossible,  although  certain  symptoms 
are  very  suggestive.  A  disease  of  acute  onset  with  nausea  and 
vomiting  and  griping  diarrhea,  especially  in  endemic  centers 
of  amebic  dysentery,  must  be  looked  upon  with  suspicion. 
Again,  a  disease  of  insidious  onset  with  chronic  diarrhea,  ema- 
ciation, etc.,  should  be  considered  at  least  possibly  amebic 
dysentery.  It  is,  however,  upon  the  microscopic  examination  of 
the  feces  or  pus  from  a  hepatic  abscess  for  the  Endamceba 
histolytica  that  the  final  diagnosis  must  rest. 

In  collecting  feces  for  examination  for  the  infecting  organism 
most  writers  enjoin  the  giving  of  a  purgative  beforehand. 
However,  as  Walker'''-  has  pointed  out,  if  a  purgative  is  given, 
the  Endamceba  histolytica,  if  present,  will  be  found  in  the  preen- 
cysted  state  when  it  most  resembles  Endamceba  coli,  and  that  if 
the  stools  are  formed,  the  organisms  are  usually  found  in  the 
encysted  state  when  they  may  most  certainly  be  differentiated 
from  Endammba  coli.  The  examination  of  dysenteric  or  diar- 
rheal stools  should  be  made  as  soon  as  possible  after  passage, 
as  entamebas  in  these  stools  are  motile  but  quickly  lose  their 
motility.  If  the  surrounding  temperature  is  much  below  that 
of  the  body  it  is  well  to  collect  the  stools  in  a  glass  jar  of  some 
description  and  place  this  in  a  vessel  of  water  at  a  temperature 
of  about  ioo°F. 

This  is  not  necessary  with  formed  stools  as  the  entamebas  are 
in  the  encysted  state  and  preserve  their  characteristics  for 
several  days.  If  the  fluid  stools  are  to  be  examined  for  the 
organisms  in  the  fresh  state,  a  platinum  loop  full  of  the  material 
is  placed  upon  a  microscope  slide  and  covered  with  a  cover- 
glass.  Gentle  pressure  should  be  applied  to  spread  the  material 
in  a  thin  layer.     If  particles  of  mucous  or  bloody  material  are 


428  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

present,  preparations  of  them  also  should  be  made.  Naturally 
it  is  more  easy  to  recognize  the  endamebas  when  they  are 
still  motile  but  after  some  experience  they  may  readily  be 
recognized  after  motility  ceases  if  disintegration  has  not 
commenced. 

A  rapid  survey  with  a  low-power  objective  should  be  made 
and  all  suspicious-looking  objects  examined  with  the  oil  im- 
mersion. When  motility  is  present  even  the  inexperienced 
should  have  little  or  no  difi&culty  in  recognizing  the  organisms. 
If,  however,  motility  has  ceased,  amebas  may  be  distinguished 
from  other  bodies  found  in  the  feces  by  their  size  which,  even 
when  smallest,  is  larger  than  pus  cells  and  other  protozoa 
except  Balantidiiim  coli,  by  their  refractiveness  which  is  greater 
than  pus  cells  or  epithelial  cells,  and  by  their  distinctness  of 
outline.  The  nucleus  of  the  ameba  is  also  characteristic  in 
that  it  is  usually  ring  shaped  and  relatively  small.  If  the 
developmental  characteristics  of  the  entamebse  are  to  be  studied, 
it  is  well  to  employ  a  warm  stage. 

In  examining  the  solid  stools  for  the  organisms  a  small  por- 
tion of  stool  is  rubbed  up  on  a  slide  with  a  drop  of  water  or  salt 
solution  and  covered  with  a  cover-glass  as  described  above. 
In  these  stools  the  amebse  are  found  in  the  encysted  state,  when 
they  are  round  or  slightly  oval,  more  refractive  than  when  in 
the  vegetative  state,  and  the  cyst  wall  is  usually  distinctly  seen. 
The  cysts  will  be  observed  to  contain  from  two  to  eight  nuclei 
depending-  upon  the  species  of  entameba  and  the  stage  of 
development. 

While  for  diagnostic  purposes  it  is  usually  best  to  examine 
the  feces  for  the  amebce  in  the  fresh  state,  it  is  sometimes  de- 
sirable for  preparing  permanent  specimens  and  for  bringing 
out  some  of  the  details  of  the  nuclei  to  stain  them. 

A  simple  method  which  is  sometimes  employed  is  to  add  a 
few  drops  of  a  weak  aqueous  solution  of  acid  fuchsin  or  methy- 
lene-blue  which  will  stain  epithelial  cells  and  debris,  leaving 
the  endameba  almost  free  from  stain. 

The  vapor  of  osmic  acid  applied  to  an  air-dried  film  of  feces 
for  twenty  minutes,  followed  by  washing  in  water,  is  another 
simple  and  satisfactory  method  of  staining. 


AMEBIC    DYSENTERY  429 

Staining  by  one  of  the  Romanowsky  modifications  is  largely 
used  and  gives  very  satisfactory  results.  The  following  method, 
originated  by  Darling  and  described  by  Deeks,'*^^  has  given  very 
good  results  in  our  hands. 

A  small  portion  of  material  is  smeared  on  a  slide  by  covering 
with  another  slide  and  drawing  the  two  apart  lengthwise,  and 
dried  in  the  air. 

The  slide  is  then  fixed  for  five  minutes  with  undiluted  Hast- 
ing's  stain,  after  which  distilled  water  is  added  until  no  more  will 
stay  on  the  slide.  The  staining  is  continued  for  one  hour. 
More  water  and  stain  may  be  added  from  time  to  time  to  pre- 
vent drying,  or  it  may  be  covered  with  a  small  bell  jar.  When 
the  staining  is  completed  the  slide  is  rinsed  in  tap  water  and 
dried,  following  which  it  is  placed  in  any  good  Giemsa  solution. 
The  one  used  by  us  is  prepared  by  mixing  5  c.c.  each  of  o.i 
per  cent,  aqueous  solution  of  yellowish  eosin  and  Azure  II  and 
diluting  with  40  c.c.  of  distilled  water. 

The  slide  is  stained  in  this  solution  over  night,  after  which 
it  is  rinsed  in  tap  water,  dried  and  differentiated  by  dipping  a 
few  times  in  60  per  cent,  alcohol  containing  i  per  cent,  aqueous 
solution  of  ammonia. 

Methods  of  dry  fixation,  however,  are  not  as  satisfactory, 
owing  to  the  distortion  of  the  nucleus,  as  certain  wet  fixation 
methods.  For  this  purpose  we  have  found  Mallory's  chloride 
of  iron-hematoxylin  stain  as  modified  by  James  and  described 
by  Craig*-^  most  satisfactory. 

1.  Thin  smears  of  material  are  immersed  without  drying  into 
Schaudinn's  sublimate-alcohol  solution  and  fixed  for  two  to 
five  minutes.  (Schaudinn's  solution  was  originally  composed 
of  one  part  of  absolute  alcohol  and  two  parts  of  saturated  aque- 
ous solution  of  bichloride  of  mercury.  It  has  been  modified 
to  contain  one  part  absolute  alcohol  to  two  parts  of  normal 
salt  solution  saturated  with  bichloride,  plus  2.5  per  cent,  glacial 
acetic  acid.) 

2.  After  fixing,  the  smears  are  hardened  in  80  per  cent, 
alcohol  for  ten  minutes. 

3.  Smears  are  washed  in  50  per  cent,  alcohol  and  then  in 
distilled  water. 


430  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

4.  Smears  are  flooded  with  a  mordant  which  consists  of 
freshly  prepared  10  per  cent,  aqueous  solution  of  chloride  of 
iron. 

5.  After  pouring  off  the  mordant  the  smears  are  flooded  with 
freshly  prepared  solution  of  hematoxylin  made  by  adding 
crystals  of  hematoxylin  to  250  c.c.  of  warm  distilled  water, 
until  a  deep  port  wine  color  is  produced.  The  stain  is  added 
to  the  slides  until  the  hematoxylin  is  precipitated,  which  is 
shown  by  the  smear  appearing  through  the  solution.  The 
staining  is  continued  for  five  to  twenty  minutes. 

6.  Following  the  staining  the  smears  are  washed  in  at  least 
ten  changes  of  distilled  water. 

7.  They  are  then  decolorized  with  freshly  prepared  0.5 
per  cent,  solution  of  chloride  of  iron  in  distilled  water. 

8.  Smears  are  washed  in  tap  water  over  night. 

9.  They  are  next  dehydrated  in  95  per  cent,  followed  by 
absolute  alcohol. 

10.  Cleared  in  xylol. 

11.  Mounted  in  neutral  balsam. 

The  cytoplasm  of  the  endamebse  stains  a  grayish  blue,  the 
nuclear  membrane  and  chromatin  a  deep  black,  while  the  struc- 
ture of  the  nucleus  is  beautifully  brought  out. 

While  it  is  necessary  to  differentiate  amebas  from  certain  other 
cells  and  artefacts  which  appear  in  the  feces,  the  main  point  in 
the  diagnosis  in  amebic  dysentery  is  the  differentiation  of 
Endamoeha  histolytica  from  Eiidamosha  coli. 

As  far  as  we  are  aware  no  one  has  reported  the  finding  of 
Endamceba  huccalis  in  the  feces,  but  it  seems  at  least  possible 
that  in  severe  cases  of  Rigg's  disease  these  organisms  might 
be  observed  in  the  feces  and  perhaps  mistaken  for  Endmnceba 
histolytica. 

The  following  table  shows  the  main  differentiating  features 
between  Endamceba  histolytica  and  Endamceba  coli: 


AMEBIC    DYSENTERY 


431 


E.  coli 

E.  histolytica 

Size 

Variable,  average  15  to  25  mi- 
crons in  diameter,  in  vegeta- 

Variable, average  25  to  40  mi- 
crons in  diameter. 

tive  stage. 

Shape 

Spheric  at  rest. 
Dull  greenish  yellow. 

Roughly  spheric  or  oval. 
Ectoplasm  hyaline,  endoplasm 
light  gray  or  greenish  tinted. 

Color 

Structure 

Ordinarily  impossible  to  differ- 

Differentiation   of    endoplasm 

entiate   between    endoplasm 

and  ectoplasm  easy,      Endo- 

and ectoplasm.     Protoplasm 

plasm  coarsely  granular. 

finely  granular. 

Nucleus 

Well  defined,   to  one  side   of 

Poorly  defined,  average  diame- 

center, 5-8  microns  in  diarne- 

ter  5  microns. 

ter,  one  or  more  nucleoli  vis- 

ible. 

Vacuoles 

Generally  absent,  generally  al- 

Always present,   may   be    nu- 

ways single,  usually  small  and 

merous,  distinct. 

indistinct. 

Motility 

Sluggish,  pseudopodia  rounded 

Active,    pseudopodia    rounded 

and  very  small. 

or  finger-like,  larger  and  more 
distinct. 

Phagocytosis  .  . 

Bacteria  and  crystals,  rarely 

In    addition    to    bacteria    and 

blood-cells. 

crystals,  red  blood-cells  often 
present. 

Cysts 

A  third  smaller  than  vegeta- 
tive forms,  limiting  wall  of 
double    outline,    protoplasm 
hyaline,      no     phagocytosis, 
eight  nuclei. 

Four  nuclei. 

Reproduction .  . 

In  vegetative  stage  by  binary 

In  vegetative  stage  by  binary 

fission  and  by  sporulation,  in 

fission,  in  cystic  stage  by  pro- 

cystic stage  by  formation  of 

duction  of  four  daughter  cells. 

slight  daughter  cells. 

In  staining  the  amebae  in  tissues  the  following  method  of 
Mallory''^-  gives  very  satisfactory  results: 

1.  Harden  in  alcohol. 

2.  Stain  sections  in  a  saturated  aqueous  solution  of  thionin 
three  to  five  minutes. 

3.  Differentiate  in  a  2  per  cent,  aqueous  solution  of  oxahc 
acid  for  one-half  to  one  minute. 

4.  Wash  in  water. 

5.  Dehydrate  in  absolute  alcohol. 

6.  Mount  in  xylol  balsam. 


432  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

By  this  method  the  nuclei  of  the  amebas,  the  granules  of 
the  amebas  and  the  granules  of  the  mastzellen  are  stained  a 
brownish  red ;  the  nuclei  of  the  mastzellen  and  of  all  other  cells 
are  stained  blue. 

Differential  Diagnosis. — There  are  a  few  conditions  which 
closely  resemble  amebic  dysentery  and  must  be  differentiated 
from  it.  The  most  important  of  these  is  bacillary  dysentery, 
which,  while  its  tendency  is  much  more  to  assume  an  acute 
form  than  amebic  dysentery,  is  usually  without  microscopic 
examination  impossible  of  differentiation  from  the  latter. 

In  amebic  dysentery  the  stools  will  almost  always  be  found 
to  contain  Endaniosha  histolytica  upon  microscopic  examination. 
If  this  organism  is  not  found  it  might  be  well  to  attempt  animal 
inoculation  as  suggested  by  Sellards  and  Baetjer.''^^  In 
bacillary  dysentery  the  B.  dysentericB  can  usually  be  recovered 
from  the  feces  by  cultural  methods,  and  in  all  but  very  mild 
cases  the  blood  serum  of  patients  suffering  with  bacillary 
dysentery  will  agglutinate  either  the  Shiga  bacillus  or  the 
Flexner  bacillus  after  seven  or  eight  days. 

Hemorrhagic  typhoid  may  be  mistaken  for  amebic  dysentery, 
especially  in  the  tropics  where  it  usually  runs  an  atypical  course. 
In  the  absence  of  amebic  in  the  stools  a  positive  blood  culture 
would  clear  up  the  diagnosis.  Later  a  Widal  test  would  be  of 
service. 

Not  infrequently  malaria  may  simulate  amebic  dysentery, 
but  an  examination  of  the  blood  should  make  it  impossible  to 
confuse  the  two  conditions,  even  in  the  absence  of  amebae  in 
the  stools. 

Tuberculosis  of  the  intestines  is  sometimes  mistaken  for  chronic 
amebic  dysentery  and  when  amebse  cannot  be  found  in  the  feces 
may  be  difficult  of  differentiation.  A  diagnostic  point  is  that 
in  tuberculosis  of  the  intestine  tenderness  is  usually  more 
marked  in  the  right  iliac  fossa,  while  in  amebic  dysentery  it  is 
usually  more  marked  over  the  sigmoid.  The  various  tubercuhn 
tests  may  be  of  value,  while  the  finding  of  the  tubercle  bacillus 
in  the  feces  will  be  conclusive. 

Malignant  involvement  of  the  sigmoid  and  rectum,  may  be  mis- 
taken for  amebic  dysentery,  and  especially  in  old  people  the 


AMEBIC    DYSENTERY  433 

rectum  should  be  examined,  when  httle  difficulty  should 
be  encountered  in  arriving  at  a  correct  diagnosis. 

The  invasion  of  the  alimentary  tract  by  other  intestinal 
parasites,  such  as  hook-worm,  may  cause  symptoms  simulating 
amebic  dysentery,  but  microscopic  examination  of  the  feces 
should  clear  up  the  diagnosis. 

The  diarrhea  of  pellagra  has  been  mistaken  for  amebic  dysen- 
tery, but  here  again  even  in  the  absence  of  the  typical  eruption 
of  pellagra  the  diagnosis  should  be  easy  upon  examination  of 
the  feces. 

It  must  be  remembered  that  it  is  not  only  possible  for  amebic 
dysentery  to  be  complicated  by  any  of  the  above-mentioned 
conditions,  but  that  such  complications  as  malaria,  pellagra 
and  hook-worm  are  by  no  means  rare. 

The  physician  should  therefore  be  upon  his  guard  to  recognize 
such  complications  by  careful  examinations  not  only  of  the 
feces  but  also  of  the  blood. 

Therapeutic  Test. — Since  the  introduction  of  emetine  into  the 
therapy  of  amebic  dysentery,  the  injection  of  this  drug  may  be 
of  importance  in  clearing  up  the  diagnosis  of  obscure  cases. 
If  the  symptoms  improve  under  such  treatment  it  would  be 
strong  presumptive  evidence  that  the  disease  is  amebic  dysen- 
tery.    If  they  do  not  improve  the  reverse  would  be  the  case. 

Hepatic  Abscess. — This  condition  following  amebic  dysentery 
may  usually  be  diagnosed  by  increase  in  size  of  the  liver,  by 
pain,  which  if  not  present  can  be  elicited  by  pressure,  by  the 
temperature  and  leucocytosis.  Or,  as  a  last  resort,  aspiration 
with  a  needle  may  be  performed.  Of  course  the  finding  of  pus 
by  aspiration  does  not  prove  the  abscess  to  be  of  amebic  origin 
and  a  search  for  the  organisms  should  be  made.  This  may  be 
done  by  similar  methods  to  those  described  above  for  feces. 

The  endamebas  are  found  in  the  aspirated  pus  of  hepatic 
abscess  in  only  about  50  per  cent,  of  cases,  but  can  be  found  in 
all  cases  by  scraping  the  wall  of  the  abscess. 


CHAPTER  XXX 
PROGNOSIS  OF  AMEBIC  DYSENTERY 

Death  in  amebic  dysentery  may  occur  from  the  gravity  of 
the  intestinal  lesions,  from  exhaustion  in  long-protracted  cases, 
from  severe  complications,  such  as  hepatic  abscess,  peritonitis 
due  to  perforation,  etc.,  from  severe  intestinal  hemorrhage,  from 
terminal  infection,  or  from  intercurrent  disease. 

The  severity  of  the  intestinal  lesions  and  hepatic  abscess  are 
the  most  frequent  causes  of  death. 

Musgrave*^®  gives  the  following  as  the  causes  of  death  of 
fifty  fatal  cases  of  intestinal  amebiasis  without  diarrhea : 

Three  from  peritonitis  following  perforation  of  the  appendix — 
two  of  these  produced  by  amebic  ulceration,  the  other  by  an 
unknown  cause,  not  amebic. 

Four  from  liver  abscess — one  perforating  into  the  right  pleura, 
one  into  the  abdominal  cavity,  and  two  without  perforation. 

One  from  acute  pericarditis. 

Eight  from  pulmonary  tuberculosis,  and  in  three  of  these 
abdominal  tuberculosis  was  also  present. 

Two  from  chronic  estivo-autumnal  fever. 

Five  from  perforation  of  amebic  ulcers  in  the  large  intestine — 
four  times  in  the  cecum  and  ascending  colon,  and  once  in  the 
transverse  colon. 

Seven  from  acute  beriberi. 

Twenty  from  lobar  pneumonia. 

Mortality. — The  mortality  in  amebic  dysentery  varies  with 
the  severity  of  the  infection,  the  time  of  beginning  treatment, 
the  resistance  of  the  patient,  and  the  method  of  treatment. 

Duncan*-^  states  that  among  sixty  cases  in  the  Niger  Protec- 
torate, of  those  treated  with  ipecac  the  mortality  was  32  per 
cent.,  while  of  those  treated  with  magnesium  sulphate  the 
mortality  was  only  2.9  per  cent.  In  the  Malay  States,  of  337 
cases  the  mortality  with  ipecac  treatment  was  31.1  per  cent., 
434 


AMEBIC    DYSENTERY  435 

with  saline  treatment  23.6  per  cent.,  while  with  boric  acid 
treatment  the  mortaUty  was  18  per  cent.  In  the  Nigri-Sembilin 
Hospital  the  mortality  sank  from  34.2  per  cent,  to  17.88  per 
cent,  after  the  introduction  of  the  boric  acid  treatment. 

Of  100  cases  treated  by  Musgrave"''  in  private  practice, 
including  all  types  and  stages  of  the  disease,  ninety-six  per- 
manently recovered  without  leaving  the  Philippines,  one  died 
and  three  returned  to  the  United  States. 

Prognosis. — In  making  a  prognosis  of  amebic  dysentery  the 
fact  of  the  great  tendency  of  this  disease  to  recur  must  be  kept 
in  mind. 

In  children,  as  a  rule,  the  prognosis  is  good,  while  in  the  aged 
it  is  bad.  It  has  been  stated  that  alcoholics  are  less  liable  to 
infection.  This  we  do  not  believe  to  be  the  case  as  the  chronic 
gastritis  so  frequently  observed  in  alcoholics  predisposes  to  the 
disease,  and  certainly  the  prognosis  in  this  class  of  individuals  is 
not  good. 

Good  general  physical  condition  and  previous  good  health 
make  for  a  favorable  prognosis. 

According  to  Musgrave''^^  the  location  of  the  lesions  is  im- 
portant as  a  prognostic  indication.  Thus  the  higher  up  the 
lesions  the  less  favorable  the  prognosis. 

The  outlook  in  cases  with  acute  onset  is  always  grave,  while  if 
the  onset  is  gradual  and  the  condition  recognized  early  the  prog- 
nosis is  good. 

Complications  will,  of  course,  render  the  prognosis  less  favor- 
able; thus  in  hepatic  abscess  the  chance  for  recovery  is  lessened, 
depending  upon  the  size  of  the  abscess. 

Strong''^''  states  that  in  twenty-seven  cases  reported  by 
Futcher  there  were  nineteen  deaths.  Of  these  cases  seventeen 
were  operated  upon  with  only  five  recoveries.  In  his  own 
cases  Strong  reports  twelve  cases  of  abscess  with  three  recov- 
eries after  operation.  One  of  us  has  operated  on  six  cases 
with  no  death. 


CHAPTER  XXXI 
PROPHYLAXIS  OF  AMEBIC  DYSENTERY 

Since  the  Endamwba  histolytica  is  primarily  an  inhabitant  of 
the  intestinal  canal  and  is  passed  with  the  feces  of  the  vast 
majority  of  patients  suffering  from  amebic  dysentery,  obviously 
one  of  the  most  important  measures  of  prophylaxis  is  the  dis- 
infection of  the  stools  in  all  cases.  This  is  best  done  by  the 
use  of  chloride  of  lime.  Bichloride  of  mercury,  i— i,ooo,  or  lo 
per  cent,  phenol  is  very  satisfactory. 

The  so-called  "carriers"  are  a  source  of  danger.  It  is  these 
individuals,  in  whom  the  organisms  exist  in  the  encysted  state 
without  any  active  manifestations  of  the  disease,  that  should  as 
far  as  possible  be  sought  out  and  treated.  It  is  obviously 
impossible  to  make  examination  of  the  feces  of  all  persons  to 
detect  carriers,  but  with  certain  units  of  population,  such  as 
in  eleemosynary  institutions,  hospitals,  prisons,  etc.,  it  is  not 
only  possible,  but  very  desirable  to  make  such  examinations. 
It  goes  without  saying  that  the  excreta  of  such  individuals 
should  be  carefully  disinfected. 

While  the  life  history  of  the  Endamceba  histolytica  outside  of 
the  human  body  is  unknown,  inasmuch  as  certain  animals, 
especially  the  cat,  are  known  to  be  capable  of  artificial  infection, 
it  is  well  within  the  range  of  possibility  that  they  may  become 
infected  without  the  intervention  of  artificial  means.  It  there- 
fore seems  to  us  that  cats  as  household  pets  should  be  eradi- 
cated from  endemic  centers  of  the  disease. 

As  stated  above,  all  authors  are  agreed  that  practically  the 
only  source  of  infection  is  by  the  ingestion  of  the  infective 
organisms,  and  in  all  probabiUty  the  main  source  of  these  is 
drinking  water.  It  therefore  becomes  an  essential  to  the  pre- 
vention of  the  disease  that  nothing  but  water  free  from  the 
amebse  be  used  for  drinking  purposes.  Obviously  in  endemic 
centers  of  amebic  dysentery  it  is  impossible  to  secure  a  raw 
436 


AMEBIC    DYSENTERY  437 

water  that  is  absolutely  above  suspicion.  It  is  therefore  advis- 
able to  boil  all  water  before  use,  and  to  store  it  in  as  nearly  a 
sterile  condition  as  possible.  It  is  well  also  to  prepare  only  a 
sufficient  quantity  for  use  for  a  short  time  at  once,  to  avoid 
possible  contamination  during  storage.  Of  course  in  endemic 
centers  the  use  of  distilled  water  or  bottled  and  carbonated 
waters  is  to  be  recommended  where  possible.  However,  care 
should  be  exercised  that  they  come  from  reliable  sources. 

The  eating  of  raw  foods  such  as  lettuce,  cress,  etc.,  is  not  to 
be  recommended. 

The  use  of  raw  milk  is  also  to  be  looked  upon  as  a  possible 
source  of  danger  in  endemic  centers,  and  unless  the  most  rigid 
sanitary  inspection  is  exercised  over  the  source  of  the  milk 
supply,  this  should  be  boiled  before  use. 

Alcohohcs  are  perhaps  more  susceptible  to  the  disease  than 
other  individuals,  therefore  the  use  of  alcohol  as  a  beverage 
should  be  interdicted. 

It  goes  without  saying  that  the  general  health  of  individuals, 
especially  those  residing  in  endemic  centers  of  amebic  dysen- 
tery, should  be  kept  as  nearly  perfect  as  possible  and  that  all 
measures  of  prophylaxis  of  other  infectious  diseases  should  be 
used. 

And,  finally,  it  is  well  to  remember  the  case  cited  above  in 
which  infection  followed  the  use  of  cold  water  enemas  and  guard 
against  such  a  possibility. 


CHAPTER  XXXII 
TREATMENT  OF  AMEBIC  DYSENTERY 

The  treatment  of  amebic  dysentery  consists  of  hygienic 
measures,  general  and  symptomatic  treatment,  surgical  pro- 
cedures, and  specific  treatment.  To  these  may  be  added  the 
surgical  and  specific  treatment  of  hepatic  abscess. 

Hygienic  Treatment. — In  the  acute  attack  of  amebic  dysen- 
tery the  patient  should  be  placed  in  bed  and  should  not  be 
permitted  to  get  up  to  urinate  or  go  to  stool,  using  the  urinal  and 
bed  pan.  The  room  should  be  well  ventilated,  but  chilling 
■draughts  of  air  which  may  increase  congestion  of  the  internal 
viscera  should  be  avoided.  In  the  chronic  course  of  the  disease 
it  is  not  necessary  for  the  patient  to  remain  in  bed,  in  fact  is 
not  desirable.  A  certain  amount  of  exercise,  depending  upon 
the  general  condition  of  the  patient,  should  be  taken,  although 
over-exertion  and  fatigue  should  be  avoided.  Care  should  be 
taken  to  avoid  exposure  to  cold  and  dampness,  and  the  clothing 
should  be  sufficient  to  keep  the  body  warm  at  all  times. 

The  diet  is  of  the  utmost  importance  in  treating  amebic  dysen- 
tery. During  the  early  acute  stage  it  should  consist  of  nothing 
but  albumin  water.  Later,  when  the  symptoms  have  shown 
some  improvement,  chicken  or  beef  broth  may  be  given.  Milk 
is  usually  contra-indicated  owing  to  its  tendency  to  form  bulky 
residue.  As  improvement  continues  soup  and  eggs  may  be 
eaten,  while  minced  chicken,  fish,  etc.,  can  usually  be  allowed 
within  a  few  days.  The  diet  in  chronic  amebic  dysentery  should 
be  sufficient  to  restore  the  body  weight,  yet  it  should  not  be 
excessive  and  should  contain  as  little  residue  as  possible.  A 
diet  composed  largely  of  meat  is  very  desirable.  There  is  little 
residue  in  such  a  diet  and  it  furnishes  a  large  amount  of  nourish- 
ment; further,  meat  stimulates  a  flow  of  the  gastric  and  intes- 
tinal juices. 

In  prescribing  a  meat  diet  care  must  be  taken  to  change  fre- 
quently the  kind  of  meat  used,  as  well  as  the  method  of  cooking 
438 


AMEBIC    DYSENTERY  439 

it.  Eggs,  tea,  small  amounts  of  toast  and  butter  are  permissi- 
ble, as  well  as  fresh  stewed  fruits  and  small  quantities  of  fresh 
cooked  vegetables. 

General  and  Symptomatic  Treatment. — In  the  acute  stages 
of  the  disease  when  griping  is  intense  and  rest  is  imperative  the 
use  of  morphine  is  to  be  recommended.  This  drug  should  be 
pushed  to  the  physiologic  limit  if  needed.  Enemas  of  lauda- 
num may  be  given.  As  the  symptoms  improve  Dover's 
powders  may  be  substituted.  Nausea  and  vomiting  when 
troublesome  may  usually  be  controlled  by  the  alkaline  carbon- 
ated waters.  Pepsin,  hydrochloric  acid  and  pancreatin  may 
be  employed  for  the  dyspepsia  seen  in  the  chronic  stages. 

If  abdominal  pain  is  severe  it  may  usually  be  relieved  by 
turpentine  stupes,  hot  fomentations  or  the  ice-bag.  It  may 
be  necessary  to  administer  opium  in  some  form  for  the  pain. 

Bismuth  was  formerly  given  quite  extensively  for  the  diarrhea, 
but  its  use  is  not  to  be  recommended. 

In  the  beginning  of  treatment,  whether  in  the  acute  or  chronic 
stage,  the  administration  of  a  dose  of  castor  oil  is  usually  ad- 
visable. This  clears  the  bowel,  and  in  a  measure,  at  least, 
assists  in  removing  the  infecting  organisms.  The  use  of  any 
purgative,  however,  is  contra-indicated  where  the  diarrhea  is 
severe  and  the  stools  thin  and  bloody. 

The  number  of  drugs  which  have  been  recommended  in 
amebic  dysentery  is  legion,  and  only  the  most  important  of 
them  can  be  mentioned. 

Copper  sulphate  and  opium  have  been  recommended  in 
chronic  dysentery.  Oil  of  turpentine  has  also  been  used  very 
extensively.  Salol,  benzosol,  benzoyl-acetyl-peroxide,  salophen 
and  many  other  similar  preparations  have  been  recommended 
and  have  had  more  or  less  extensive  use. 

The  use  of  rectal  injections  of  various  drugs  for  their  ame- 
bacidal  action  has  been  widely  recommended.  After  a  pre- 
liminary douche  of  warm  water  to  cleanse  the  lower  bowel  the 
injection  of  the  drug  at  a  temperature  of  about  96°?.  is  made. 

Solutions  of  quinine  have  been  extensively  employed  for 
this  purpose  since  the  time  of  Loesch.  This  drug  is  usually 
used  in  a  i  to  1,500  dilution  and  about  i  liter  injected.     Argy- 


440  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

rol  has  been  highly  recommended  in  i  per  cent,  solution,  while 
thymol,  potassium  permanganate,  silver  nitrate,  protargol,  boric 
and  tannic  acids,  creosote,  etc.,  have  had  more  or  less  vogue. 

Surgical  Treatment. — Several  surgical  procedures  have  been 
advocated  in  the  treatment  of  amebic  dysentery.  For  the 
most  part,  however,  they  have  been  recommended  only  in  the 
most  severe  cases  and  those  which  have  not  yielded  to  other 
methods  of  treatment.  According  to  Herrick,^-'' White,  in  1895, 
was  the  first  to  suggest  surgical  treatment  in  this  disease. 
This  worker  recommended  making  an  artificial  anus  on  the 
right  side  for  the  purpose  of  giving  the  colon  rest  and  to  ad- 
minister local  treatment  in  severe  cases  of  ulcerative  colitis. 
Later  other  writers  advocated  cecostomy  and  appendicostomy 
with  lavage  of  the  colon  with  various  antiseptics,  such  as  argyrol, 
silver  nitrate,  potassium  permanganate,  etc. 

In  certain  extreme  cases  of  amebic  dysentery  where  the  struc- 
ture of  the  colon  has  been  very  extensively  destroyed  and  the 
patient  almost  moribund,  the  excision  of  the  entire  colon  has 
been  performed. 

Specific  Treatment. — While,  as  mentioned  above,  certain 
drugs  such  as  quinine,  salol,  etc.,  have  been  injected  rectally  for 
the  purpose  of  destroying  the  infecting  organisms,  they  are  not 
considered  true  specifics.  Ipecac,  however,  has  been  employed 
as  a  specific  for  dysentery  for  over  two  centuries.  This  drug 
was  first  known  in  Europe  in  1672,  having  been  brought  from 
Brazil  where  it  was  used  by  the  natives  as  an  emetic.^^^  John 
Helvetius,  grandfather  of  the  famous  author  of  that  name, 
used  it  so  successfully  in  the  treatment  of  the  Dauphin  that 
he  was  given  a  large  sum  of  money  and  public  honors  by  Louis 
XIV  upon  the  condition  that  he  make  the  nature  of  his  treat- 
ment public.  While  in  Europe  the  use  of  ipecac  fell  into  dis- 
repute, it  was  employed  with  considerable  success  in  India,  and 
in  1858  Docker,  an  English  army  surgeon,  brought  it  again  into 
prominence  by  advising  its  use  in  comparatively  large  doses. 
It  has  since  that  time  been  used  with  varying  success  in  nearly 
all  countries  where  amebic  dysentery  is  known.  The  usual 
method  of  procedure  in  administering  ipecac  is  to  instruct  the 
patient  to  abstain  from  food  for  three  or  four  hours,  and  about 


AMEBIC    DYSENTERY  44I 

twenty  minutes  after  giving  a  dose  of  ten  to  twenty  drops  of 
laudanum  to  give  20  to  60  grains  of  the  powdered  ipecac  root, 
usually  in  capsules.  After  this  the  patient  is  instructed  to  lie 
on  his  back  in  bed,  absolutely  quietly  for  at  least  four  hours. 
Should  nausea  and  vomiting  of  the  drug  be  caused  within  an 
hour  he  should  receive  another  dose  as  soon  as  the  nausea  ceases. 

The  main  objection  to  the  ipecac  treatment  of  amebic  dysen- 
tery has  been  that  in  doses  sufficiently  large  to  exert  any  specific 
action  nausea  and  vomiting  are  almost  sure  to  occur.  Even 
the  pills  coated  with  substances  insoluble  in  the  stomach  do 
not  entirely  overcome  this  effect. 

The  real  specific  treatment  of  amebic  dysentery  may  be  said 
to  have  begun  with  the  introduction  of  emetine  for  this  purpose. 

This  drug  is  one  of  the  alkaloids  of  ipecac  discovered  in  1867 
by  Pelletier  and  has  the  formula  C15H22NO2.  It  is  a  white 
amorphous  powder  with  a  melting  point  of  6o°C.  With  the 
halogens  and  with  nitric  acid  it  forms  crystaUine  salts.  It  is 
readily  soluble  in  chloroform,  ether,  benzol  or  alcohol.  Its 
solution  in  the  latter  gives  no  coloration  with  ferric  chloride. 
Emetine  is  insoluble  in  solutions  of  caustic  or  carbonated  alka- 
lies, but  is  soluble  in  acetic  acid  in  which  latter  it  effects  no 
substitution.  The  most  frequently  employed  salt  of  emetine 
is  the  hydrochloride  (C15H22NO2CI2H2O). 

The  first  use  of  emetine  in  amebic  dysentery  is  accredited 
to  Walsh,*^'  who  in  1891  employed  it  in  combination  with 
Mayer's  reagent.  He  reported  34  cases  diagnosed  clinically, 
treated  in  this  manner,  of  which  32  were  clinically  cured  in 
an  average  of  4.9  days,  one  was  unimproved  and  one  died.  It 
was  not  until  twenty  years  later  that  any  scientific  work  was 
done  to  determine  the  action  of  emetine  on  the  amebae.  In 
191 1  Vedder,"*^^  working  with  cultures  of  the  free  living  amebas, 
showed  that  ipecac  in  dilutions  of  i  to  10,000  to  i  to  50,000  was 
amebecidal,  and  deematized  ipecac  in  dilution  of  i  to  5,000  was 
not  amebecidal,  while  emetine  in  dilution  of  i  to  100,000  killed 
the  amebcC. 

To  Rogers, *^^  however,  is  due  the  credit  of  applying  emetine, 
clinically  to  amebic  dysentery.  This  worker  first  found  that 
solutions  of  emetine  hydrochloride  in  normal  saline  in  dilutions 


442  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

of  I  to  10,000  immediately  killed  the  active  pathogenic  amebae 
(£.  histolytica)  present  in  mucus,  and  that  in  dilutions  of  i  to 
100,000  they  were  rendered  inactive  and  were  apparently  killed. 
After  these  experiments  Rogers  tried  the  drug  hypodermically 
in  cases. of  amebic  disease  and  reported  most  favorably  upon 
it.  In  twenty-four  cases  treated  in  this  manner  twenty  were 
cured,  two  moribund  patients  died  within  three  days  after 
admission  to  the  hospital,  and  two  died  from  other  diseases 
following  the  cure  of  the  dysentery.  The  average  time  in  the 
hospital  was  7.2  days,  while  the  average  time  until  the  stools 
became  normal  was  2.35  days. 

Following  the  brilliant  results  of  Rogers  many  investigators 
have  used  emetine  in  the  treatment  of  amebic  dysentery,  with 
such  generally  favorable  results  that  there  can  be  no  doubt 
that  this  drug  should  rank  as  a  specific  with  quinine  in  malaria 
and  mercury  and  salvarsan  in  s3^hiUs. 

The  dosage  employed  by  Rogers  was  )^  to  i  grain  of  the  hydro- 
chloride dissolved  in  about  i  c.c.  of  salt  solution  administered 
hypodermically.  This  amount  has  been  increased  by  various 
workers  up  to  5-6  grains.  Baermann  and  Heinemann''^''  rec- 
ommend the  subcutaneous  or  intravenous  injection  of  one  or 
two  doses  of  2^3  to  3  grains,  followed  in  the  next  eight  or  ten 
days  by  four  or  five  subcutaneous  injections  of  i3^-2  grains 
given  at  intervals  of  two  or  three  days  according  to  the  results  of 
examination.  According  to  these  authors  this  after-treatment 
should  be  repeated  at  intervals  of  three  or  four  weeks  and  the 
stools  should  be  examined  carefully  for  amebs  at  frequent 
intervals  for  several  months. 

We  consider  that  for  ordinary  cases  such  doses  are  too  large 
and  prefer  to  give  not  more  than  i  grain  daily,  best  in  two  in- 
jections, one  in  the  morning  and  one  at  night.  This  seems  as 
effective  as  the  larger  doses  and  much  less  irritating. 

In  administering  emetine  intravenously  the  dose,  not  to 
exceed  0.25  gram  (3.8  gr.)  per  60  kilograms  (132  pounds)  of 
body  weight,  should  be  given  in  about  100  c.c.  of  normal  salt 
solution.  This,  to  our  minds,  is  the  method  of  choice  in  acute 
cases.  Emetine  may  be  given  by  mouth,  but  is  neither  as 
effective  nor  as  pleasant  to  take,  as  nausea  and  vomiting  are 


AMEBIC    DYSENTERY  443 

much  more  liable  to  occur.  And  further,  the  drug  is  more  or 
less  irritating  to  the  intestinal  mucosa. 

Nausea  and  vomiting  are  rare  following  the  subcutaneous  and 
intravenous  injection  of  emetine  except  in  very  large  doses 
(s-6  grains). 

Depending  upon  the  size  of  the  dose  there  is  some  local  reac- 
tion at  the  point  of  injection  when  the  subcutaneous  route  is 
used,  and  a  general  urticaria  has  been  noted. 

Hepatic  Abscess. — If  the  hepatic  abscess  be  small,  it  will 
probably  usually  yield  to  the  general  emetine  treatment  alone. 
Rogers^-^  early  reported  the  aspiration  of  liver  abscess  and  the 
injection  of  the  cavity  with  i  grain  of  emetine  dissolved  in  i 
ounce  of  normal  salt  solution.  This  with  small  and  medium 
sized  abscesses  is  usually  sufficient,  but  with  large  abscesses  a 
radical  operation  may  be  necessary,  although  Cantlie^"  con- 
siders" cutting"  operations,  "  overheroic  "  and  that  better  results 
are  obtained  by  the  use  of  a  large  trocar  and  canula.  A  recent 
case  treated  by  one  of  us  was  promptly  cured  after  evacuation 
of  the  pus  and  daily  injections  of  J^  grain  of  emetine. 

The  operations  most  frequently  employed  are  the  abdominal 
and  transthoracic.  The  former  is  employed  when  the  abscess  is 
in  the  lower  portions  of  the  liver  and  the  latter  when  it  is  found 
in  the  superior  portions  or  extends  into  the  thorax. 

The  abdominal  operation  is  performed  by  placing  the  patient 
on  his  back  or  if  a  lateral  incision  is  necessary  on  his  left  side.  A 
sand  bag  is  placed  under  him  to  raise  the  liver  up  as  close  to  the 
abdominal  wall  as  possible.  An  incision  8  to  lo  cm.  in  length 
over  the  most  prominent  part  of  the  swelling  is  made  through 
the  skin  and  superficial  fascia  and  is  deepened  to  the  peritoneum. 
If  adhesions  exist  between  the  abscess  wall  and  the  peritoneum, 
walling  off  the  abscess  from  the  peritoneal  cavity,  the  abscess 
may  be  opened  at  once.  If,  however,  no  adhesions  are  present, 
a  series  of  sutures  are  made  between  the  capsule  and  some  of  the 
liver  substances  and  the  parietal  peritoneum  and  part  of  the 
rectus  muscle.  The  peritoneum  is  walled  off  with  a  thick  layer 
of  gauze,  after  which  an  incision  is  made  into  the  abscess  cavity 
and  the  pus  allowed  to  escape.  Some  authorities  advocate  the 
use  of  a  cautery,  but  this  is  usually  unnecessary.     After  the 


444  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

evacuation  of  the  pus  the  abscess  cavity  may  be  washed  out 
with  normal  salt  solution  followed  by  2  or  3  grains  of  emetine 
dissolved  in  several  ounces  of  salt  solution.  A  large  drainage 
tube  is  now  inserted  and  anchored  with  two  stitches  to  the 
skin. 

In  performing  the  transthoracic  operation  an  incision  8  to  10 
cm.  in  length  is  made  along  the  rib  under  which  the  abscess  seems 
to  be.  This  incision  should  separate  skin,  fascia,  muscle  and 
periosteum.  The  latter  is  separated  from  the  bone  with  a 
periosteal  elevator  for  about  8  cm.  and  the  rib  cut  at  either  end 
of  the  incision  with  bone  forceps  or  a  saw.  The  same  care 
must  be  taken  not  to  contaminate  the  pleura  as  was  advocated 
for  protection  of  the  peritoneum.  The  remainder  of  the  opera- 
tion is  performed  in  a  similar  manner  to  the  abdominal 
operation. 

Other  complications,  such  as  severe  hemorrhage,  a  perito- 
nitis, and  intercurrent  disease  must  be  met  and  dealt  with  as  if 
the  amebic  infection  did  not  exist. 


HOOK-WORM  DISEASE 


CHAPTER  XXXni 
INTRODUCTION 

Uncinariasis,  ankylostomiasis,  tropical  chlorosis,  tunnel 
workers'  anemia,  brickmakers'  anemia,  mountain  cachexia, 
miners'  anemia,  dirt-eating  disease,  etc. 

History. — Uncinariasis  is  a  parasitic  infestation  with  certain 
species  of  hookworm  and  is  characterized  by  the  discharge  of 
ova  and  worms  in  the  feces,  progressive  anemia,  and  digestive 
and  nervous  phenomena. 

There  is  to  be  found  in  the  Ebers  papyrus,  written  by  the 
Egyptians  about  1550  B.  C,  a  reference,  thought  by  Joachim 
and  Sandwith,  to  relate  to  hook-worm  infection.  The  authen- 
ticity of  this  reference  must  of  necessity  remain  doubtful  owing 
to  the  incompleteness  of  the  chnic  picture. 

The  earliest  undoubted  accounts  of  this  disease  are  those  of 
Piso,  in  Brazil,  in  1648,  Pere  Labot  of  Guadeloupe  in  his  travel 
narratives  in  1742,  and  Bryon  Edwards  in  1793,  in  his  history 
of  the  British  Colonies  in  the  West  Indies.  The  latter  who  was 
a  planter  in  Jamaica  for  many  years  attributed  a  large  propor- 
tion of  the  deaths  among  the  negroes  to  this  disease.  Following 
these  were  numerous  reports  by  English,  French  and  Danish 
practitioners  in  the  West  Indian  Islands  and  in  Guiana. 

The  etiology  of  the  condition  was  completely  dark  until  the 
paper  of  Dubini  in  1843.  From  1838  this  observer  at  several 
autopsies  had  discovered  these  little  worms  to  which  he  attrib- 
uted the  production  of  chronic  diarrhea. 

Castaglioni  found  the  parasite  in  Milan  in  1844.  Pruner  in 
Egypt  mentioned,  in  1846,  that  he  had  found  it  in  cachectic, 
scrofulous  and  dropsical  adults,  but  he  failed  to  note  any 
etiologic  relationship. 

445 


446  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Bilharz  discovered  independently  the  worms  in  Egypt  in 
1852,  and  it  was  with  him  that  Griesinger  estabHshed  the  fact 
that  the  hook-worm  caused  the  disease  which  he  declared  affected 
one-fourth  of  the  population  of  Egypt. 

Wucherer  in  Brazil  in  1866  called  attention  to  the  prevalence 
of  the  disease  in  that  country  and  succeeded  in  arousing  some 
interest. 

In  Italy  Paletti  and  Maliverria,  in  1877,  suggested  that 
brickmakers'  anemia  was  due  to  hook-worm  infection  and  in  the 
same  year  recognized  in  the  feces  the  typical  ova  of  the  parasite, 
and  attributed  grave  results  to  the  blood-sucking  propensities 
of  the  parasite. 

The  epidemic  occurring  in  1879  among  the  workers  of  the  St. 
Gothard  tunnel  marks  an  epoch  in  the  prophylaxis  of  the  disease. 
Hundreds  of  these  laborers  sickened  and  many  died;  no  cause 
was  known,  and  gases,  faulty  ventilation  and  lack  of  sunshine 
were  advanced.  Colormiatti  found  i  ,500  uncinarias  in  the  intes- 
tines of  one  of  the  dead  laborers.  As  a  result  of  the  investi- 
gation which  followed  the  true  cause  was  determined,  and  to 
Perroncito  and  Bozzolo  is  given  the  credit  for  the  campaign 
against  the  epidemic. 

Profiting  by  the  lessons  of  this  epidemic,  investigations  were 
then  made  into  the  anemia  of  mines  and  brickyards  of  Europe 
with  the  uniform  result  of  finding  the  hook-worm  responsible. 

For  more  than  100  years  anemia  has  been  recognized  as  the 
scourge  of  Porto  Rico.  On  August  8,  1899,  a  hurricane  swept 
a  part  of  the  island.  Ashford,  of  the  Army  Medical  Corps,  was 
ordered  to  establish  a  provisional  hospital  for  the  care  of  some  of 
the  sick  natives  who  were  thronging  the  streets.  Blood  exami- 
nations of  these  natives  showed  an  eosinophilia  which  led  to 
an  examination  of  the  feces  disclosing  the  ova  of  the  parasites 
responsible  for  the  trouble.  On  November  24,  1899,  Ashford 
wired  the  chief  surgeon  of  his  findings.  This  culminated  in  the 
appointment  of  the  Porto  Rico  Anemia  Commission,  which  has 
contributed  much  toward  the  eradication  of  the  infection 
from  the  island  and  toward  the  scientific  study  of  the  disease. 

In  the  United  States  the  earliest  reference  which  seems  to 
allude  to  hook-worm  infection  is  that  of  Pitt,  in  1808,  writing  of 


HOOK-WORM    DISEASE  447 

the  Roanoke  Valley  in  North  Carohna.  Chalbert,  in  Louisiana, 
in  1832,  Cotting,  in  Georgia,  in  1836,  Le  Conte,  in  Georgia,  in 
1845,  Little,  in  Florida,  in  1845,  ^.nd  Duncan,  in  Louisiana,  in 
1850,  refer  to  what  was  probably  uncinariasis. 

Blickhahn,  of  St.  Louis,  in  1893,  is  apparently  the  first  in  this 
country  to  observe  and  recognize  as  such,  a  case  of  hook-worm 
infection.  His  patient  was  a  German  brickmaker  who  had  been 
in  America  but  seventeen  months,  and  it  is  probable  that  the 
infection  was  imported. 

In  1893,  Allen  J.  Smith,  of  Galveston,  Texas,  found  ova  of 
hook-worm  in  a  specimen  of  feces  but  was  unable  to  locate  the 
patient.  Cases  were  reported  from  Buffalo,  N.  Y.,  by  Mohlau  in 
1897;  from  Richmond,  Va.,  by  Gray  in  1901 ;  from  New  Orleans, 
by  Tebault  in  1899;  from  Galveston,  Texas,  by  Smith  in  1901; 
from  Washington,  D.  C,  by  Clayton  in  1901 ;  from  St.  Louis,  by 
Dyer  in  1901;  from  Georgia,  by  Claude  Smith  in  1902;  and  by 
Harris  in  1902. 

The  credit,  however,  for  the  discovery  that  hook-worm  is 
endemic  in  the  Southern  States  belongs  to  Stiles.  Upon  the 
evidence  of  specimens  from  Washington,  D.  C,  from  Porto 
Rico,  sent  by  Ashford,  from  Cuba,  sent  by  Guiteras,  and  from 
Galveston,  sent  by  Smith  he  stated  positively  in  a  paper  pub- 
lished September  25,  1902,  that  there  existed  in  the  United 
States  an  endemic  uncinariasis,  which  had  been  generally  over- 
looked. He  was  thereupon  commissioned  by  the  Public  Health 
and  Marine  Hospital  Service  to  investigate,  and  after  a  prelimi- 
nary survey  in  Virginia,  North  Carolina  and  South  Carolina  he 
reported,  October  22,  1902,  that  the  disease  was  resulting  in  loss 
of  wages,  loss  in  productiveness  of  the  farms,  loss  in  the  school 
attendance  of  the  children,  etc.  He  announced  also  that 
the  parasite  was  a  new  species  which  he  termed  uncinaria 
americana. 

Stiles'  observations  were  abundantly  confirmed  from  many 
sections  and  great  interest  was  aroused,  the  matter  being- dis- 
cussed pro  and  con  in  the  lay  press.  The  concern  culminated 
in  the  organization  on  Oct.  26,  1909,  of  the  Rockefeller  Sanitary 
Commission,  financed  by  John  D.  Rockefeller,  for  a  campaign 
against  the  endemic  in  the  South. 


44o  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Geographic  Distribution. — Uncinariasis  does  not  occur  north 
of  latitude  52°,  and  north  of  47°,  it  is  found  only  in  the  hospitable 
warmth  of  mines.  Thus  it  is  a  disease  of  tropic  and  subtropic 
countries,  but  there  are  countries  with  endemic  foci  in  more 
northerly  climes. 

In  Germany  the  Westphalia  mining  districts  are  heavily 
infested.  The  disease  prevails  also  in  localities  in  Rhenish 
Prussia.  Cases  have  been  reported  from  other  parts  of  Prussia. 
In  Austria  and  Hungary  the  disease  has  been  known  to  be 
prevalent  for  many  years,  particularly  among  miners,  but  among 
other  classes  as  well.  From  Limburg  in  Holland  several  cases 
have  been  recorded.  The  Belgian  mines  are  hot  beds  of  infec- 
tion where  public  measures  have  been  directed  against  the  sup- 
pression of  the  disease.  In  France,  Auzin,  Vallenciennes,  Com- 
mentry,  Lyons  and  St.  Etienne  are  centers  of  infection.  Uncin- 
ariasis is  said  to  occur  in  the  Spanish  mines  and  in  Servia' 
and  Bulgaria.  In  Italy,  Sicily,  and  Sardinia  the  disease 
prevails  extensively.  In  the  Dolcoath  coal  mine  in  Cornwall, 
England,  nearly  20  per  cent,  of  the  miners  have  been  found 
infested. 

In  Asia  a  number  of  the  Indian  Provinces,  particularly  Bengal, 
Madras,  and  Travancore  are  scourged.  It  has  been  stated  that 
in  Ceylon  the  ravages  of  the  hook-worm  exceed  those  of  cholera. 
Siam,  Indo-China,  Korea,  and  portions  of  China  are  intense 
foci.  In  Japan  the  mountainous  regions  of  the  island  of 
Kiou-Siou  are  said  to  be  intensely  infested.  The  disease 
prevails  in  the  Malay  States  and  is  found  in  the  Province  of 
Bagdad. 

The  continent  of  Africa,  especially  the  coast  regions  are  foci 
of  hook-worm  infection.  Parts  of  Egypt  are  heavily  scourged. 
Abyssinia,  German  East  Africa,  Nyassaland,  British  Central 
Africa  and  Orange  Free  State  show  a  high  infection  index. 
British  South  Africa,  parts  of  Cape  Colony,  and  Madagascar 
are  infested.  In  the  north,  besides  Egypt,  Tunis  and  Algeria 
habor  the  disease.  On  the  west  coast  it  prevails  from  the  Senegal 
River  to  the  Congo  River. 

In  AustraHa  the  infection  is  known  upon  the  west  coast 
particularly  in  Queensland.     Other  islands  where  the  disease 


HOOK-WORM    DISEASE  449 

is  known  to  be  endemic  are  the  Leeward  Islands,  Comore 
Islands,  Mauritius,  New  Guinea,  Borneo,  Java,  Sumatra,  Fiji, 
Sandwich  Islands,  West  Indies,  Samoa,  Formosa,  Philippines 
and  Guam. 

In  South  America  the  disease  has  been  studied  particularly 
in  Brazil.  Paraguay  and  northern  Argentine  are  endemic  foci. 
Other  South  American  States  where  the  infection  prevails  are 
Bolivia,  Peru,  Ecuador,  Columbia,  Venezuela  and  Guyana. 

Central  American  States  from  which  cases  are  reported  are 
Panama,  Costa  Rica,  Nicaragua,  Salvador,  Guatemala,  and 
British  Honduras. 

Cases  have  been  found  in  southern  Mexico  and  in  Lower 
California. 

In  the  United  States  the  disease  is  endemic  in  all  the  states 
south  of  the  Ohio  and  Potomac  Rivers,  and  in  Arkansas, 
Louisiana  and  Texas.  Autochthonous  cases  have  been  re- 
ported from  Oklahoma,  Nevada,  California  and  Missouri 
and  it  is  probable  on  clinical  grounds  that  the  disease  exists  in 
Maryland. 

To  illustrate  the  extent  of  infection  in  some  of  the  Southern 
States  the  following  is  quoted  from  the  1912  Report  of  the 
Surgeon  General  of  the  U.  S.  Pubhc  Health  Service: 

"Hook-worm  infection  has  been  demonstrated  in  93  of  the 
100  counties  in  Virginia;  in  99  of  the  100  counties  in  North 
Carolina;  in  140  of  the  146  counties  of  Georgia;  in  every  county 
in  South  Carolina;  in  66  of  the  67  counties  in  Alabama;  in  77 
of  the  79  counties  in  Mississippi;  in  27  of  the  59  parishes  of 
Louisiana;  in  57  of  the  75  counties  in  Arkansas;  in  95  of  the  96 
counties  in  Tennessee;  in  22  of  the  119  counties  in  Kentucky. 
The  foregoing  statistics  include  the  reports  up  to  December  31, 
191 1,  as  reported  by  the  state  boards  of  health  in  question. 
Of  the  884  counties  in  these  ten  states,  infection  has  been  dem- 
onstrated by  the  state  boards  of  health  in  719;  the  remaining 
156  counties  had  not  been  surveyed  when  these  statistics  were 
summarized." 

The  comparative  degree  of  infection  at  all  ages  in  eleven 
states  is  shown  in  the  following  table  from  the  1913  Report  of 
the  Rockefeller  Sanitary  Commission: 
29 


450 


ENDEMIC   DISEASES   OF   THE    SOUTHERN   STATES 


Alabama 

Arkansas 

Georgia 

Kentucky 

Louisiana 

Mississippi 

Nortii  Carolina. 
South  Carolina. 

Tennessee 

Texas 

Virginia 


Total. 


25,821 
17,169 
31,251 
64,485 
35,472 
110,007 
247,870 
47,692 
32,432 
38,913 
49,622 


700,734 


11,204 
4,151 
I9,°34 
22,862 
17,533 
42,722 
77,625 
16,386 
10,369 
13,447 
12,888 


S,22I 


The  new-world  hook-worm,  Necator  americanus,  besides  being 
the  parasite  of  the  disease  in  the  United  States,  has  been  found 
in  Porto  Rico,  Cuba,  Guam,  Panama,  Brazil,  Philippine  Islands, 
Australia,  Ceylon,  Mysore,  Burmah,  Assam,  Cochin  China, 
China,  Egypt,  Rhodesia,  Gold  Coast,  Uganda,  and  South 
Africa.     Imported  cases  have  been  recorded  in  Italy  and  Spain. 


CHAPTER  XXXIV 
ETIOLOGY  OF  HOOK-WORM  DISEASE 

Climate. — As  has  been  stated  hook-worm  disease  is  one  of 
tropic  and  subtropic  climates  with  occasional  endemic  foci  in 
temperate  climates,  these  latter  being  chiefly  in  mines.  It  has 
been  determined  that  temperatures  from  78.5°  to  95°F.  are 
best  adapted  to  the  hatching  of  ova  and  that  while  they  still 
matured  below  7i°F.  their  numbers  were  few  and  many  perished. 
Direct  exposure  to  sunlight  inhibits  the  development  of  the 
ova.  Altitudes  from  the  sea  level  to  3,000  feet  are  had  by 
endemic  areas. 

Season. — In  cold  weather  larval  life  and  activity  are  dimin- 
ished or  abolished  and  the  hook-worm  larva  is  no  exception. 
Freezing  prevents  ova  from  hatching  but  they  may  develop 
after  gentle  thawing  out.  Infection  in  temperate  chmates  is 
commoner  in  the  summer  months. 

Moisture. — Moisture  is  necessary  for  the  development  of 
both  ova  and  larvae.  Complete  desiccation  destroys  both  ova 
and  larvae.  The  ova  will  not  develop  in  water  but  Lambinet-"' 
has  shown  they  will  then  enter  a  resistant  state  and  hatch  later 
under  favorable  circumstances.  Bruns'-""  experiments  show 
that  (i)  in  undiluted  feces  the  larvas  appeared  in  four  days  but 
in  ten  days  all  were  dead;  (2)  the  best  cultures  were  obtained 
from  a  dilution  of  from  i :  10  to  1:100;  (3)  dilutions  of  from 
1 :  1 ,000  to  1 : 2 ,000  killed  the  larvae  and  prevented  the  ova  from 
developing  after  six  days. 

Soil. — The  character  of  the  soil  exerts  an  important  influence 
on  the  distribution  of  the  disease.  Stiles^"'  has  shown  that  in 
the  South  the  infection  prevails  chiefly  upon  sandy  soils.  My 
experience  in  eastern  Arkansas  was  that  alluvial  soil  did  not 
afford  a  favorable  environment  and  this  conclusion  is  further 
strengthened  by  the  work  of  the  Rockefeller  Sanitary  Com- 
mission. The  Porto  Rico  Anemia  Commission-"-  found  that 
4SI 


452  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

sandy  regions  were  not  those  which  contributed  the  majority 
of  their  cases  on  that  island. 

Race. — It  was  shown  by  Zinn  and  Jacoby"  that  the  negro 
possesses  a  relative  immunity  to  the  effects  of  hook-worm  in- 
fection. It  is  probable,  however,  that  negroes  in  the  Southern 
States  are  more  frequently  infested  than  whites.  Hence  the 
carrier  problem  is,  as  in  malaria,  a  weighty  one.  No  immunity 
other  than  racial  is  known. 

Sex. — Stiles-"*  believes  the  infection  to  be  commoner  in 
females  than  in  males  in  the  South.  In  Egypt  Sandwith^"^ 
found  only  i  per  cent,  of  his  cases  in  females.  Of  89,219  cases 
examined  by  the  Porto  Rico  Anemia  Commission  52.10  per 
cent,  were  males  and  47.90  per  cent,  were  females.-"^ 

Age. — In  the  Southern  States  the  disease  is  commoner  in 
the  young,  58.5  per  cent,  of  Stiles'-"'*  cases  being  in  children 
under  sixteen  years  old.  Two  years  experience  of  the  Porto  Rico 
Commission-"'  gave  the  following  age  distribution: 

Under  10  years 15,622 

10  to  20  years 50.924 

'21  to  30  years 36,589 

31  to  40  years 18,254 

41  to  50  years 8,796 

51  to  60  years 3,841 

Over  60  years 1,413 

Of  18,865  cases  found  by  this  Commission-"*  in  1905  there 
were  240  under  five  years  of  age.  Sandwith's-"^  youngest 
patient  was  four  years  old,  Giles'-"''  four  years  old,  and  Stiles 
reports  one  in  a  child  of  three. 

Occupation. — Those  occupations  which  necessitate  intimate 
relations  with  the  soil  predispose  to  hook-worm  infection. 
Miners  and  brickmakers  are  the  classes  chiefly  infested  in 
Europe.  In  the  South  the  agriculturists  are  especially  predis- 
posed, particularly  those  who  go  into  the  fields  barefoot  or 
poorly  shod.  Dock  and  Bass^"'  mention  cases  occurring  in 
charcoal  burners  and  turpentine  dippers.  The  cotton  mill 
operatives  through  the  South  are  heavily  infested,  but  this  is 
probably  due  more  largely  to  the  insanitary  condition  of  their 
homes  than  to  the  occupation. 


HOOK-WORM    DISEASE  453 

Social  Condition. — While  no  class  is  exempt  from  infection 
those  who  use  concrete  sidewalks  and  modern  sewerage  are 
far  less  frequently  infested  than  those  who  walk  the  fields  and 
defecate  in  the  fence  corners.  Uncinariasis  is  chiefly  a  disease 
of  poverty,  ignorance  and  bad  hygiene.  Surface  closets  and 
soil  pollution  are  largely  responsible  for  the  dissemination  of 
the  disease,  hence  its  over-whelming  prevalence  in  the  rural 
districts. 

Mode  of  Infection. — There  are  two  routes  by  which  the  para- 
sites gain  access  to  the  host,  through  the  mouth  and  through 
the  skin. 

There  is  no  doubt  that  the  former  method  is  more  common 
than  is  supposed  by  some  authorities.  Infection  through  un- 
clean vegetables,  fruits  and  drinking  water,  and  soiled  hands 
undoubtedly  occurs.  A  considerable  proportion  of  hook-worm 
patients  in  this  country  deny  having  had  ground  itch,  and 
while  some  of  these  may  have  been  unaware  of  an  existing 
dermatitis,  it  cannot  be  denied  that  many  of  them  are 
correct. 

In  1898  while  working  in  his  laboratory  in  Cairo  Looss  inad- 
vertently allowed  a  drop  of  water  containing  more  than  i,ooo 
hook-worm  larvae  to  fall  between  the  fingers.  This  was  im- 
mediately followed  by  burning  and  redness.  To  be  sure  that 
the  symptoms  were  due  to  the  fluid  he  permitted  another  drop 
to  fall  upon  another  part  of  his  hand  and  this  was  followed  by 
the  same  results.  Examining  the  fluid  remaining  upon  his 
hand  he  found  that  most  of  the  larvte  had  disappeared  leaving 
behind  a  few  sluggish  ones  and  numerous  empty  sheaths.  In 
due  time  ova  were  found  in  the  feces  and  anemia  and  debility 
ensued  necessitating  prolonged  treatment  with  thymol. 

Looss'  next  experiment  was  upon  the  leg  of  a  boy,  one  hour 
before  the  leg  was  amputated.  After  thorough  cleansing  a 
drop  of  fluid  containing  larvae  was  placed  on  the  skin.  After 
amputation  the  skin  was  removed,  hardened  and  sectioned. 
The  larvce  were  found  in  the  skin  having  penetrated  through 
the  hair  follicles. 

Another  experiment  was  made  upon  a  volunteer  nurse  who 
was  infected  through  the  forearm.     Ova  were  found  in  the 


454  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

feces  seventy-one  days  later.  Looss  succeeded  in  infecting 
puppies  in  a  similar  manner. 

These  experiments  with  ankylostoma  duodenale  were  con- 
firmed by  Schaudinn  in  Germany,  Herman  in  Belgium,  and 
others. 

The  same  mode  of  infection  was  proven  for  Uncinaria  ameri- 
cana  by  Claude  Smith  of  Atlanta.  A  mixture  of  soil  and  feces 
containing  larvae  was  bound  upon  the  wrist  of  a  volunteer.  In 
five  minutes  a  sharp  stinging  sensation  was  complained  of. 
During  the  night  and  the  next  day  the  itching  was  severe,  and 
the  area  was  covered  with  vesicles.  These  crusted  and  des- 
quamated and  by  the  eighth  day  had  disappeared.  By  the 
middle  of  the  sixth  week  ova  were  found  in  the  feces. 

After  piercing  the  skin  through  the  hair  follicles  the  larvae 
gain  entrance  to  the  circulation  and  are  carried  through  the 
heart  to  the  lungs.  Here  they  leave  the  blood-vessels,  entering 
the  air  cells,  traverse  the  bronchi  to  the  larynx,  and  down  the 
esophagus  through  the  stomach  to  the  intestine.  From  the 
entrance  into  the  skin  until  ova  appear  in  the  feces  averages 
from  five  to  ten  weeks. 

The  dermatitis  produced  by  the  entrance  of  the  larvae  into 
the  skin  is  known  as  "ground  itch."  Its  commonest  location 
is  upon  the  feet  and  ankles,  oftenest  between  the  toes,  but 
may  occur  upon  any  part  of  the  body  exposed  to  infection. 
Turner^^"  states  that  in  the  South  African  mines  the  miners 
sitting  on  damp  wood  contracted  the  sores  on  their  buttocks. 

The  Parasite. — While  Looss  succeeded  in  infecting  dogs  with 
human  hook-worms  both  through  the  skin  and  through  the 
mouth,  this  parasite  is  not  known  in  nature  to  infest  any  host 
but  man.  Uncinariasis  is  known  to  occur  in  many  domestic 
and  other  animals  but  their  parasites  are  not  communicable  to 
man. 

The  new-world  hook-worm,  Uncinaria  americana,  or  Necator 
americanus,  has  a  cylindrical  body,  narrowed  anteriorly  and  of 
a  light  reddish  or  grayish  color.  The  male  measures  from  7  to 
9  mm.  in  length,  and  0.3  to  0.35  mm.  in  diameter;  the  female 
9  to  II  mm.  in  length  by  0.4  to  0.45  mm.  in  diameter.  The 
buccal  capsule  is  small,  presents  an  irregular  border  and  is  pro- 


HOOK-WORM   DISEASE 


455 


vided  with  a  ventral  pair  of  prominent  semilunar  plates,  there 
being  dorsally  a  pair  of  slightly  developed  chitinous  plates. 
The  dorsal  tooth  projects  prominently  into  the  buccal  cavity. 
The  four  buccal  lancets  are  situated  deeply.     The  tail  of  the 


Fig.  86. — Ova  of  uncinaria  americana,  enlarged. 


male    flares    into    an    umbrella-like    caudal 
bursa,  composed  of  dorsal  and  ventral  lobes 
and  prominent  lateral  lobes   supported   by 
rays  like    the   ribs   of   an    umbrella.      Two 
barbed  spicules  proceed  from  the  bottom  of 
the  caudal  bursa  and  the  genital  organ  lies 
at  the  bottom.       The  tail  of  the  female  is 
conical.     The  vulva  is  situated  slightly  an- 
terior to  the  middle  of  the  body.     The  eggs 
are  symmetrically  oval  and  vary  from  64  to 
76  microns  in  length  by  36  to  40  microns  in 
breadth.     They  are  laid  in  a  state  of  segmentation,  the  number 
of  segments  being  most  commonly  four. 

The  old-world  hook-worm  is  longer  and  broader,  the  mouth  is 
heavily  armed  bearing  two  pairs  of  ventral  teeth,  curved  like 


worm  larva,  Infective 
stage,  enlarged. 


456  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


Fig.  88. — Uncinaria  americana, 
male,  enlarged. 


Fig.  89. — Uncinaria  americana, 
female,  enlarged. 


(      ) 


Fig.  go.^Showing  natural  size  of  hook-worms,     a,  Male;  b,  female. 


HOOK-WORM    DISEASE  457 

hooks,  and  one  pair  of  dorsal  teeth,  the  buccal  capsule  is  larger, 
and  the  ova  are  smaller. 

The  ova  never  hatch  in  the  intestine,  but  pass  out  with  the 
feces.  The  ova  hatch  under  proper  conditions  in  from  one  to 
three  days  or  less,  into  rhabditiform  larvae,  measuring  about 
0.2  mm.  in  length.  In  a  few  days  the  larvae  attain  a  length  of 
0.5  to  0.6  mm.  and  moult.  On  the  fifth  to  the  ninth  day  a 
second  moult  or  ecdysis  occurs  and  the  larvffi  are  in  the  infec- 
tive stage  or  stage  of  encystation,  and  measure  0.65  mm.  long 
by  0.025  to  0.027  mm.  broad.  The  larvae  may  live  for  months 
in  this  stage  but  cannot  reach  maturity  except  in  the  intestine 
of  man.  They  arrive  at  maturity  from  four  to  six  weeks  after 
infection.  The  third  stage  in  the  evolution  of  the  larva  marks 
the  beginning  of  its  parasitic  existence.  Its  sojourn  in  the 
stomach  is  said  not  to  exceed  fifteen  hours.  During  the  fourth 
stage  the  mouth  parts  are  further  elaborated,  a  provisional 
buccal  capsule  appearing,  and  the  sexes  are  differentiated. 
In  the  fifth  or  adult  stage  all  the  organs  become  maturely 
developed. 

These  parasites  infest  the  small  intestine,  chiefly  the  duo- 
denum and  jejunum,  but  the  ileum  may  also  harbor  them. 

The  number  of  parasites  varies  greatly  and  is  not  necessarily 
in  ratio  to  the  severity  of  the  disease.  In  40  cases  of  the 
Porto  Rico  Commission-"*  in  which  the  worms  expelled  were 
counted,  they  varied  from  96  to  4,395.  Of  a  series  observed  by 
Leichtenstern-^^  in  9  cases  the  parasites  were  less  than  100, 
in  14  cases  between  100  and  500,  in  3  cases  over  500,  num- 
bering respectively  991,  1,066,  and  2,763.  Turner-^-  states  that 
in  his  experience  in  South  Africa  it  was  exceptional  to  collect 
50  specimens  from  one  body.  Of  58  cases  reported  from  North 
Carolina  by  Stiles-'^^  the  greatest  number  of  worms  was  2,277, 
the  smallest  number,  i,  the  average  135. 

With  reference  to  the  proportion  of  sexes  of  the  parasites 
existing  in  given  cases,  Bilharz  found  the  proportion  of  males 
as  I  to  3;  Leichtenstern  as  10  to  24;  Lutz  as  2  to  3;  Schulthess 
as  I  to  6;^^^  Sandwith-"^  reports  that  in  about  50  cases  the  pro- 
portion of  males  to  females  was  56  to  44.  Stiles-'^  observed 
102  cases  from  which  13,080  parasites  were  obtained;  46  per 


458  ENDEMIC   DISEASES    OF    THE    SOUTHERN    STATES 

cent,  of  the  specimens  were  males  and  53  per  cent,  females. 
Of  the  102  cases,  37  presented  an  excess  of  males,  9  presented 
an  equal  number  of  males  and  females,  and  56  presented  an  ex- 
cess of  females. 

Pathogenesis. — A  satisfactory  explanation  of  the  proximate 
cause  of  the  symptoms  of  uncinariasis  is  yet  lacking.  There 
are  three  factors  which  may  be  concerned  in  the  pathogenesis: 
(i)  The  abstraction  of  blood  by  the  parasite  and  hemorrhage 
subsequent  thereto;  (2)  mechanical  injury  to  the  intestinal 
mucosa  followed  by  infection;  (3)  the  production  of  a  toxin. 

1.  The  structure  of  the  mouth  parts,  the  habit  of  the  worms 
clinging  to  the  mucosa,  a  portion  of  which  it  partially  swallows, 
and  the  finding  of  blood  in  the  alimentary  canals  of  the  para- 
sites renders  it  certain  that  the  hook-worm  is  a  blood  sucker. 
It  is  furthermore  possible  that  the  worm  injects  a  substance  at 
the  site  of  feeding  to  prevent  the  coagulation  of  blood  to  cause 
it  to  flow  more  easily  as  the  leech  and  mosquito  are  supposed  to 
do.  This  is  rendered  probable  by  the  finding  of  visible  and 
occult  blood  in  the  feces,  by  the  appearance  of  the  mucosa,  and 
by  experiments  of  Loeb  and  Smith. -"'■'  It  seems  hardly  possible 
that  the  amount  of  blood  merely  consumed  by  the  parasites  in 
certain  cases  of  light  infection  could  account  for  the  symptoms 
present  so  that  subsequent  bleeding  or  some  other  factor  must 
be  at  work  in  these  cases. 

Looss  claims  that  the  mucous  membrane  itself  is  the  food 
of  the  hook-worm  and  that  the  abstraction  of  blood  is  only 
accidental. 

2.  The  mechanical  wounding  of  the  intestine  and  ensuing 
infections  may  possibly  play  a  role  in  the  pathogenesis  of  hook- 
worm disease  but  nothing  definite  is  known. 

3.  The  belief  that  a  toxin  is  produced  "by  the  parasite  and  is 
responsible  for  the  symptoms  is  widespread.  The  reasons  for 
this  theory  are: 

(a)  The  blood  changes,  eosinophilia,  almost  or  quite  normal 
red  cell  count  with  low  hemoglobin  percentage. 

(b)  Nervous  symptoms  out  of  proportion  to  the  anemia 
and  which  may  improve  before  the  anemia  has  been  com- 
pensated. 


HOOK-WORM   DISEASE  459 

(c)  The  relative  immunity  evinced  by  certain  individuals  and 
races. 

{d)  Analogy  to  other  helminth  infestations. 

(e)  The  appearance  of  symptoms  before  the  parasites  have 
reached  the  suctorial  phase. 

(/)  Symptoms  in  some  cases  out  of  proportion  to  the  number 
of  worms. 

{g)  Deposits  in  liver  and  kidney  cells  giving  reaction  of  hema- 
toidin. 

{h)  Results  of  experiments. 

The  question  of  the  existence  of  a  toxin,  however,  is  far  from 
settled.  A  toxin  is  said  to  have  been  demonstrated  by  the 
experiments  of  Bohland-"^,  Lussano,^^'  Micheli,-"^  Crisapilli,-"^ 
de  Renzij-o^  Preti,2«2  Tenholt  and  Peiper,^"  Arslanj^^^  Battis- 
tiner^^  Gabbi  and  Vadala.^os  Goldman,^''^  Muller.^es  Rieder,^^^ 
Gappert,2«='  Ehrlich,2«3  Leichtenstern^es  and  Herman,^*"'  while 
Loeb  and  Smith, ^o^  and  Whipple, 2*''  on  the  basis  of  their  ex- 
periments deny  the  existence  of  a  toxin. 


CHAPTER  XXXV 
PATHOLOGY  OF  HOOK-WORM  DISEASE 

Even  in  severe  cases  the  body  usually  shows  no  emaciation. 
The  skin  is  pallid  and  anemic.  The  subcutaneous  fat  is  well 
preserved  and  of  a  light  yellow  color.  Edema  is  commonly 
present,  ascites  is  shown  in  greater  or  less  degree,  hydrothorax 
and  hydropericardium  are  often  found  and  the  condition  may 
amount  to  general  anasarca.  The  muscles  appear  anemic  and 
may  be  atrophied  or  normal  in  development. 

The  stomach  is  often  dilated  and  sometimes  the  seat  of  gas- 
tritis. Hemorrhagic  erosions  of  the  mucosa  have  been  observed. 
Hook-worms  are  occasionally  found  in  this  organ  either  free  or 
attached. 

Important  changes  are  shown  in  the  intestine.  The  duode- 
num, jejunum,  and  part  of  the  ileum  are  in  a  catarrhal  condition, 
thickly  coated  with  mucus  in  which  the  worms  are  embedded. 
This  part  of  the  bowel  may  be  studded  with  erosions  produced  by 
the  bites  of  the  parasites.  Sometimes  these  may  be  visible 
to  the  naked  eye  and  sometimes  they  may  show  through  the 
serosa.  There  are  usually  more  erosions  than  parasites.  Free 
blood  is  rarely  found  in  the  bowel  but  the  mucus  may  be  blood 
stained.  The  majority  of  the  parasites  appear  in  the  upper  and 
middle  third  of  the  jejunum.  Interstitial  inflammation,  infil- 
tration of  the  solitary  follicles  and  Peyer's  patches,  and  atrophy 
of  the  valvulae  conniventes  are  microscopic  findings  in  many 
cases. 

The  liver  is  commonly  of  normal  size.  In  color  it  is  very 
pale  being  of  a  light  brownish-yellow  color.  On  section  it  is 
soft,  greasy  and  friable.  These  changes  depend  upon  fatty 
degeneration  which  is  present  in  practically  every  case.  The 
outer  third  of  the  lobule  is  chiefly  affected  where  the  entire  lobule 
is  not  involved.  Yellow  pigment  and  dilated  capillaries  have 
been  found  in  a  few  cases.  Amyloid  degeneration  is  a  rare 
phenomenon. 

460 


HOOK-WORM    DISEASE  46 1 

The  pancreas  is  anemic  but  further  changes  are  not  constantly 
found. 

The  spleen  may  be  slightly  enlarged  but  is  more  often  normal 
in  size  or  atrophied.  In  the  Porto  Rico  Commission's^"^  autop- 
sies microscopic  sections  revealed  a  great  reduction  of  lymphoid 
elements  and  a  decrease  in  the  protoplasm  of  the  cells.  The 
size  of  the  Malpighian  corpuscles  was  greatly  reduced,  the  cells 
were  scanty  and  widely  separated,  and  the  central  artery 
showed  hyaline  degeneration.  The  increase  of  connective 
tissue  was  only  relative  and  apparent.  Pigmentation  is  rare. 
Changes  in  the  hemolymph  glands,  particularly  those  about  the 
bifurcation  of  the  abdominal  aorta,  have  been  described.  These 
are  larger  than  normal,  of  a  dull  reddish  hue  and  on  section 
show  mitosis  and  phagocytosis  of  red  cells. 

The  marrow  of  the  long  bones  presents  changes  similar  to 
those  of  pernicious  anemia,  being  reddish  and  soft,  and  in  ad- 
dition showing  groups  of  eosinophiles  and  an  abundance  of 
myeloplaxes. 

Cardiac  hypertrophy  is  a  common  post-mortem  finding. 
Flabby  musculature  and  fatty  degeneration  predispose  to 
valvular  incompetency.  An  increase  in  the  pericardial  fat  is  not 
infrequent.     Arteriosclerosis  is  often  found. 

In  the  lungs  extreme  pallor  and  edema  are  almost  constant 
changes.  Passive  congestion  is  a  finding  in  many  cases.  Pleu- 
ral effusion  is  present  in  the  majority  of  cases. 

Practically  all  cases  show  chronic  parenchymatous  or  diffuse 
nephritis.  The  kidneys  are  usually  slightly  enlarged.  The 
convoluted  tubules  show  the  most  marked  changes  consisting 
of  fatty  degeneration  and  desquamation  of  epithelium.  Yel- 
low pigment  is  a  rare  finding. 

The  brain  usually  shows  an  intense  anemia  and  effusion  into 
the  ventricles  of  a  clear,  pale  yellow  fluid. 


CHAPTER  XXXVI 

CLINICAL  HISTORY  OF  HOOK-WORM  DISEASE 

Classifications  of  clinical  forms  of  hook-worm  disease  are  purely 
arbitrary  and  rest  solely  on  differences  of  degree.  Lutz-*^  has 
proposed  the  following  rather  complicated  schedule : 

I.  Stage  of  exclusively  local  symptoms. 

(a)  Acute  form. 

(b)  Chronic  form.  In  the  two  forms  the  symptoms  are  simi- 
lar and  characterized  by  disorders  of  digestion;  no  pallor  nor 
acceleration  of  pulse. 

II.  Stage  of  anemia. 

(a)  Acute  form.  i.  First  degree:  the  vessels  of  the  con- 
junctiva are  visible,  the  nails  and  the  lips  are  pale,  the  pulse  is 
frequent,  no  anemic  murmur.  2.  Second  degree:  conjunctiva 
colorless,  nails  and  lips  pale,  pulse  always  accelerated,  anemic 
murmur. 

(b)  Chronic  form.  Anemia  more  or  less  intense,  cardiac 
hypertrophy  and  dilatation,  valvular  insufficiency  rare,  pulse 
rapid. 

III.  Dropsical  stage. 

(a)  Acute  form.  Profound  anemia,  rapid  pulse,  anemic 
murmur,  edema  and  serous  effusion. 

(b)  Chronic  form.  Symptomsof  organic  dissolution,  arrhyth- 
mic heart,  myocarditis,  asystole,  cyanosis,  anasarca,  marasmus, 
death. 

Ashford  and  King's'-"^  division  into  slight,  moderate,  and 
marked  cases,  and  Stiles'-"'  into  light,  medium,  and  severe  are 
much  simpler  and  more  satisfactory. 

Light  cases  are  those  in  which  the  feces  contain  a  few  ova,  but 
symptoms,  if  present,  are  slight.     Anemia  is  not  particularly 
noticeable,  but  fatigue  is  out  of  proportion  to  exertion  and  there 
may  be  slight  uneasiness  in  the  epigastrium. 
462 


HOOK-WORM    DISEASE 


463 


Moderate  cases  are  those  in  which  there  are  definite  anemia 
and  digestive  disorders  with  their  resulting  symptoms. 

In  severe  cases  symptoms  of  the  first  two  forms  are  intensely 
exaggerated,  the  heart  weakens,  and  edema  and  ascites  super- 
vene. 

A  not  altogether  fanciful  classification  of  the  stages  of  hook- 
worm disease  is  into  primary,  secondary  and  tertiary,  after  the 
stages  of  syphilis.     The  primary  stage  is  the  stage  of  the  initial 


Fig.  91.  —.1.  Delia  Carder,  tlrant  County,  Arkansas,  aged  sixteen,  practically 
an  invalid  from  childhood,  treated  for  malaria  and  tuberculosis,  found  heavily 
infected  with  hook-worms,  treated.  B.  Delia  Carder  as  she  is  today.  (Rocke- 
feller Sanitary  Commission.) 

lesion  or  port  of  entry  of  the  organisms  into  the  host — ground 
itch.  The  period  of  incubation  of  this  stage  is  from  a  few  hours 
to  a  few  days.  This  is  followed  by  a  secondary  period  of  incu- 
bation, as  in  syphilis,  during  which  time  the  parasites  are  imma- 
ture and  unable  to  produce  marked  symptoms.  The  secondary 
stage  begins  after  the  parasites  have  reached  the  alimentary 


464  ENDEMIC   DISEASES    OF   THE    SOUTHERN    STATES 

canal,  have  matured,  and  have  begun  to  produce  ova  in  the  feces, 
anemia  and  digestive  disorders.  As  tertiary  symptoms  may  be 
designated  evidences  of  organic  changes  in  other  organs  resulting 
in  heart  weakness  and  anasarca. 

General  Description. — It  is  ordinarily  from  five  to  ten  weeks 
from  the  time  the  larvae  enter  the  skin  until  ova  appear  in  the 
feces. 

The  symptoms  are  essentially  those  of  anemia  and  impaired 
digestion.  A  slight  uneasiness  in  the  epigastrium  is  often  the 
first  symptom,  or  the  patient  may  complain  of  indigestion. 
Pressure  often  increases  the  uneasy  sensation  or  causes  actual 
pain,  while  it  may  be  relieved  by  food.  The  appetite  is  not 
radically  affected  early  but  is  apt  to  be  capricious.  Gastralgic 
pains  may  be  complained  of.  Meteorism  appears  in  many  cases 
and  abdominal  tenderness  is  not  infrequent.  The  bowels  are 
constipated  or  regular,  occasionally  loose.  In  mild  cases  nausea 
and  vomiting  are  not  early  symptoms.  A  certain  degree  of 
pallor,  as  evidenced  by  bloodless  conjunctivae  and  pale  mucous 
membranes,  is  observed  in  all  but  mild  cases.  The  skin  is  dry 
and  inactive.  Headache  is  a  common  complaint  and  dizziness 
is  frequent.  The  patient  is  subject  to  palpitation  and  shortness 
of  breath  on  slight  exertion  and.  this,  with  muscular  weakness, 
gives  him  an  aversion  to  labor.  In  chronic  cases  the  mentality 
is  substandard,  initiative  and  ambition  are  lacking,  and  the 
victim  is  insensitive  to  the  stimuli  of  the  daily  routine  of  life. 
Hence  it  is  that  the  hook-worm  has  been  called  the  "germ  of 
laziness."  In  severe  cases  the  pulse  is  accelerated  and  weak, 
the  blood  pressure  is  low,  and  the  anemia  reaches  a  low  degree. 
An  anemic  murmur  is  often  heard  over  the  precordia  and  the 
heart  may  be  dilated.  There  are  pains  in  the  thorax  and 
joints.  The  appetite  becomes  perverted  and  the  patient  eats 
earth,  chalk  or  soot.  Sometimes  blood  is  passed  from  the 
bowels.  The  face  becomes  puffy,  the  ankles  swell  and  fluid 
may  collect  in  the  serous  cavities. 

Hook-worm  disease  in  childhood,  if  neglected,  results  in  re- 
tarded mental  and  physical  development.  The  children  are 
over-age  in  school.     Puberty  is  delayed. 

Sandwith-""  found  that  100  infested  men  weighed  17.5  pounds 


HOOK-WORM    DISEASE  465 

less  than  normal.  Dock  and  Bass-"''  report  that  fifty-six  grown 
men  affected  with  hook-worm  disease  averaged  8}^  pounds 
lighter  and  2^3  inches  shorter  than  normal. 

The  duration  of  the  disease  in  untreated  cases  is  governed 
by  two  factors,  the  opportunity  for  reinfection  and  the  life  of 
the  worm.  It  is  evident  that  there  is  no  limit  to  the  number  of 
reinfections  nor  the  duration  of  cumulative  infections  in  the 
absence  of  prophylaxis.  As  to  the  life  of  the  parasite  it  is 
certain  that  this  may  be  as  long  as  twelve  or  fifteen  years. 

The  cause  of  death  is  most  commonly  exhaustion.  Inter- 
current affections  play  a  prominent  role.  Fatty  degenerations 
are  frequent  as  secondary  factors.  Exodus  may  occur  from 
intestinal  perforation. 

Temperature. — This  is  normal,  subnormal  or  elevated.  I 
have  noted  nothing  characteristic  in  its  occurrence  or  course. 
In  Porto  Rico,  fever  at  the  onset  of  the  disease  is  said  to  be  a 
fairly  constant  symptom.-"^  In  Ceylon,  Castellani-^^  observed 
fever  in  about  25  per  cent,  of  the  cases  of  medium  gravity  and 
in  50  to  75  per  cent,  of  those  of  a  serious  nature.  Sandwith-"^ 
in  Cairo  found  that  one-third  of  his  patients  had  a  normal 
temperature  during  their  stay  in  the  hospital  and  that  two- 
thirds  had  a  distinctly  subnormal  range.  In  cases  having 
fever  it  rarely  exceeds  102°. 

Skin. — Ground  itch,  known  also  as  dew  poison,  toe  itch  and 
water  itch,  is  usually  the  first  evidence  of  the  disease.  It 
occurs  of  tenest  between  the  toes  and  on  the  sides  and  tops  of  the 
feet,  but  may  appear  upon  the  hands,  buttocks,  or  indeed  upon 
any  portion  of  the  skin.  Its  commonest  site  is  explained  by 
the  habit  of  going  barefoot,  and  squeezing  mud  between  the 
toes.  Its  first  appearance  is  of  small  macules  or  papules  which 
soon  proceed  to  vesiculation  and  pustulation.  Scratching  and 
mechanical  irritation  follow,  producing  crusts  and  scabs.  It 
is  highly  probable  that  bacterial  infection  occurs  both  with  the 
entry  of  the  larvffi  and  later  when  the  lesions  are  scratched. 
The  exudate  from  the  ruptured  lesions  is  sticky  and  causes  the 
stockings  or  bandages  to  adhere  tightly.  The  average  duration 
of  ground  itch  is  one  or  two  weeks,  but  deeply  ulcerated  lesions, 
particularly  between  the  toes,  sometimes  take  weeks  in  healing. 


400  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

The  pallor  of  the  skin  varies  from  a  fish-belly  white  through 
yellowish  to  tan.  True  icterus  is  rare.  It  should  be  borne 
in  mind  that  it  is  impossible  to  determine  the  degree  of  anemia 
by  the  appearance  of  the  skin. 

Edema  is  present  in  many  moderate  and  most  severe  cases. 
In  the  absence  of  heart  and  kidney  lesions  its  frequency  is  in 
direct  ratio  to  the  degree  of  anemia.  It  is  commonest  in  the 
lower  extremities,  then  in  the  face.  The  entire  body  may  be 
water-logged  in  severe  cases.  Of  the  serous  cavities  the  peri- 
toneal is  oftenest  involved.  Injuries  of  the  skin  usually  heal 
slowly  and  may  result  in  ugly  ulcers. 

Diminished  activity  of  the  skin,  indicated  by  lack  of  perspira- 
tion, is  a  common  manifestation.  Atrophy  of  the  skin  results 
from  chronic  infections. 

Petechias  are  occasionally  observed  in  those  of  low  vitality. 
Urticaria  is  an  infrequent  symptom.  Pruritus  is  not  uncom- 
mon. 

Digestive  System. — A  vague  uncomfortableness  in  the 
epigastrium  is  rarely  absent  except  in  the  mildest  cases.  Sen- 
sations of  weight  and  distention  after  eating  are  the  rule. 
Gnawing  pain  is  frequently  complained  of  and  gastralgia  is 
sometimes  present.  Not  infrequently  the  epigastric  region  is 
tender  to  pressure,  a  sign  of  significant  diagnostic  import. 

The  tongue  is  furred,  enlarged  and  shows  the  imprints  of  the 
teeth.  Not  infrequently  a  purplish  smear  is  observed  on  each 
side  of  the  tongue  as  if  a  pencil  had  been  sucked.  This  ap- 
peared in  nearly  5  per  cent,  of  a  series  of  cases  reported  from 
Porto  Rico.^"^  These  phenomena  are  attributed  to  engorge- 
ment of  the  veins.  Pharyngitis  may  occur  early.  Catarrhal 
stomatitis  is  occasionally  observed. 

The  appetite  is  very  variable.  It  is  said  to  be  frequently  greatly 
increased  in  the  beginning,  but  in  cases  seen  in  practice  it  is 
usually  capricious  or  diminished.  In  severe  cases  it  is  nearly 
always  diminished. 

One  of  the  most  striking  features  of  the  disease  is  geophagy 
or  dirt-eating.  This  runs  the  scale  from  the  desire  for  coarse 
food  to  actual  dirt-eating.  It  was  formerly  thought  to  be  the 
cause  of  the  anemia.     Among  the  many  articles  which  may  be 


HOOK-WORM    DISEASE  467 

eaten  are  coffee,  chalk,  ashes,  soot,  brittle  wood,  paper,  earth, 
mortar,  clothing,  sand,  etc.  I  have  known  subjects  to  walk 
12  miles  and  back  to  obtain  a  small  box  of  a  certain  kind  of 
earth.  I  am  convinced,  however,  that  this  is  not  pathog- 
nomonic of  uncinariasis  and  that  it  is  a  habit  which  is  widely 
prevalent  among  the  negro  women  of  the  South. 

Flatulence  and  heart-burn  are  common  complaints.  Nausea 
is  infrequent  in  mild  cases  but  common  in  severe  infections. 
Vomiting  may  occur  in  severe  cases.  Hematemesis  is  occasion- 
ally reported. 

Yoshida^"^  states  the  results  of  his  observations  upon  loi  sub- 
jects as  to  the  acidity  of  the  gastric  juice  as  follows: 

1.  The  content  of  free  hydrochloric  acid  in  the  gastric  juice 
in  uncinariasis  is  usually  normal,  then  follows  hypochlorhydria, 
then  hyperchlorhydria. 

2.  The  greater  the  intensity  of  the  anemia  the  lower  the  con- 
tent of  free  hydrochloric  acid. 

3.  The  appetite  is  usually  in  the  most  intimate  relation  to  the 
content  of  free  hydrochloric  acid. 

The  bowels  are  usually  constipated  or  irregular,  often  normal, 
occasionally  loose  or  even  dysenteric.  Blood  is  not  often  ob- 
served macroscopically  in  the  feces.  Of  over  22,000  speci- 
mens of  feces  examined  by  the  Porto  Rico  Commission,-"'  only 
six  contained  blood  and  five  blood  and  mucus  from  a  naked- 
eye  inspection.  Microscopically  blood  is  occasionally  noted. 
Charcot-Leyden  crystals  are  not  infrequently  found. 

The  chief  characteristic  of  the  feces  in  these  cases  is  of  course 
the  presence  of  hook-worm  ova.  These  vary  greatly  in  numbers 
and  may  be  present  in  every  field,  or  several  slides  may  have  to 
be  examined  before  finding  a  single  specimen.  Leichtenstern'^ 
states  that  it  is  not  unusual  for  a  single  stool  to  contain  four  mil- 
lion ova.  The  number  of  ova  in  the  feces  is  a  guide  to  the 
number  of  parasites  in  only  a  very  general  way,  if  at  all. 

Adult  parasites  are  very  exceptionally  found  in  the  feces 
except  after  the  administration  of  a  proper  anthelmintic. 

Circulatory  System. — In  mild  cases  the  only  symptoms  from 
the  circulatory  system  are  palpitation  and  acceleration  of  the 
pulse  on  exertion.     Pain  in  the  precordial  region  is  common  in 


46b  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

the  more  severe  cases.  This  pain  may  be  lancinating  or  may 
be  dull.  In  the  mildest  cases  the  pulse  rate  may  not  depart 
from  the  normal  except  after  exertion,  but  in  moderate  and 
severe  cases  it  is  always  accelerated.  It  is  usually  soft  and 
compressible,  even  dicrotic,  and  later  may  become  small  and 
irregular.  The  blood  pressure  is  low.  In  mild  cases  the  apex 
beat  is  normal  in  location  and  force.  Later  it  is  apt  to  be  dis- 
placed downward  and  to  the  left,  and  diffuse  and  weak. 
Pulsation  in  the  epigastrium  is  often  observed.  Acute  dilata- 
tion and  cyanosis  have  been  observed.  An  anemic  murmur  is 
the  rule  when  the  hemoglobin  per  cent,  is  markedly  reduced. 
Insufficiency  from  dilatation  also  may  cause  characteristic 
murmurs.  Dilatation  is  not  uncommon  in  chronic  infections 
and  hypertrophy  may  result.  Pericardial  effusion  often  occurs 
in  the  cases  with  anasarca.  Exaggerated  pulsations  in  the  neck 
and  throbbing  in  the  supraclavicular  spaces  may  be  detected 
at  a  distance.  The  superficial  abdominal  veins  are  often  dis- 
tended. Uncinariasis  in  childhood  predisposes  to  organic  heart 
lesions  in  later  years  and  probably  also  to  arteriosclerosis. 

Upon  the  blood  is  spent  most  of  the  force  of  the  infestation. 
In  mild  cases  there  may  be  no  reduction  of  red  cells.  Dock  and 
Bass^°'-.examined  forty  university  students  who  were  hook-worm 
carriers  and  found  the  average  number  of  red  cells  to  be  5,246,- 
322.  However,  there  is  usually  a  reduction  of  these  cells. 
The  average  count  is  around  three  millions,  though  it  may  run 
in  severe  cases  below  one  million. 

The  most  frequent  qualitative  changes  in  the  erythrocytes 
are  polychromatophilia,  poikilocytosis,  and  the  appearance 
of  microcytes  and  macrocytes.  Nucleated  red  cells  are  not 
rarely  present.  Notwithstanding  these  changes  occur,  they  are 
not  as  prevalent  as  in  primary  anemia. 

The  hemoglobin  falls  more  rapidly  and  to  a  lower  degree  than 
the  red  cells  so  that  the  color  index  is  nearly  always  below  nor- 
mal. It  is  occasionally  noted  that  the  color  index  is  high,  even 
as  high  as  1.35  having  been  observed.  In  the  mildest  infections 
there  may  be  little  or  no  reduction.  The  average  in  this  country 
is  perhaps  between  40  and  60  per  cent.  The  Porto  Rico  Com- 
mission report  one  case  in  which  it  was  as  low  as  9  per  cent.,  and 


HOOK-WORM   DISEASE  469 

they  record  it  that  persons  with  as  low  as  1 6  to  20  per  cent,  can 
and  do  keep  at  their  accustomed  labor. -"^ 

The  white  cells  range  from  5,000  to  10,000  per  cubic  milli- 
meter. Leucopenia  is  common  in  cases  of  long  standing  and 
leucocytosis  may  usually  be  accounted  for  by  complications. 
The  increase  in  the  eosinophiles  is  the  only  characteristic 
change  in  the  leucocyte  formula.  This  is  the  rule  in  mild  and 
moderate  cases,  but  eosinophilia  is  usually  lacking  in  severe 
and  fatal  cases.  Ehrlich  and  Leichtenstern-^^  report  a  case 
where  these  cells  were  72  per  cent,  of  the  total  leucocytes.  The 
highest  count  of  Dock  and  Bass^"'  was  34  per  cent.,  mine  was 
26  per  cent.  Fifteen  per  cent,  is  not  uncommon  for  moderate 
cases.  Regarding  the  variation  of  the  eosinophiles  the  Porto 
Rico  Commission  draw  the  following  conclusions: 

1.  Very  severe  chronic  cases  with  poor  resisting  power  and 
exhausted  blood-making  organs  have  little  or  no  eosinophilia. 

2.  A  rise  in  eosinophiles  is  generally  found  in  cases  which 
progress  favorably  and  should  influence  the  prognosis. 

3.  If  very  severe  cases  presenting  little  or  no  eosinophilia  fall 
in  their  eosinophile  percentage  without  improving  in  their  gen- 
eral condition,  the  prognosis  for  such  a  case  is  less  favorable. 

Under  appropriate  treatment  the  eosinophiles  rise  to  a  vary- 
ing degree,  then  gradually  fall  to  normal. 

Extreme  blood  changes  are  much  less  frequently  found  in 
the  negro  race  than  in  the  white. 

Respiratory  System. — Symptoms  on  the  part  of  the  respira- 
tory system  are  few.  Dyspnea  is  very  common  and  usually  in 
proportion  to  the  anemia.  Hydrothorax  often  occurs  in  ana- 
sarca cases  and  edema  of  the  lung  may  supervene.  Bronchitis 
is  mentioned  by  some  observers  as  an  early  symptom  and  at- 
tributed to  the  passage  of  the  larva:  through  the  air  cells  and 
bronchi,  but  I  have  had  no  experience  with  this  symptom.  So 
far  as  I  am  aware  larvae  have  not  been  found  in  the  sputa. 

Urinary  System. — In  cases  of  edema  or  anasarca  attended 
with  grave  anemia  it  is  often  difficult  to  determine  how  much 
of  the  former  are  attributable  to  the  anemia  and  how  much 
to  the  kidneys.  That  nephritis  does  play  a  role  is  credible  from 
both  clinic  and  urinary  findings. 


470  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

In  the  early  stages  the  quantity  of  urine  is  normal;  later  it 
becomes  diminished.  The  Porto  Rico  Commission^"^  deter- 
mined that  one-fourth  of  cases  of  all  grades  have  albuminuria. 
Casts  are  not  very  frequent  and  when  present  are  in  relatively 
small  numbers.  The  kinds  of  casts  found  are  in  the  order  of 
frequency  hyaline,  granular,  fatty  and  epithelial.  Urobihn 
and  indican  are  common  findings.  Biliary  coloring  matters 
are  not  common. 

Generative  System. — Puberty  is  delayed  in  both  sexes.  The 
male  organs  are  apt  to  remain  undeveloped.  Impotence  is 
very  common.  In  the  Porto  Rico-"''  cases  58.5  per  cent,  of  the 
males  were  completely  impotent,  and  9.7  per  cent,  were  par- 
tially so.  In  Sandwith's-""  series  63  per  cent,  were  completely 
impotent  and  13  per  cent,  were  partially  so. 

The  age  at  which  menstruation  begins  is  often  postponed 
several  years.  Irregularity  of  the  menses  is  very  common. 
Total  suppression  of  the  menses  is  not  uncommon  in  moderate 
cases  and  is  the  rule  in  severe  ones.  Sterility  is  frequent. 
Stiles^^^  showed  that  of  thirty-four  pregnancies  in  hook-worm 
subjects  8.1  per  cent,  terminated  in  miscarriage.  Still-births  are 
said  to  cause  havoc  among  the  women  of  Porto  Rico.  Lactation 
may  be  impaired  or  suppressed  in  severe  cases. 

Musciilar  System. — The  muscles  are  weak  and  lack  tone. 
Fatigue  on  exertion  is  due  not  only  to  dyspnea  but  to  muscular 
weakness.  To  this  weakness  is  largely  attributable  the  reputa- 
tion for  laziness  which  the  subjects  of  uncinariasis  have.  Pains 
in  the  joints  and  bones,  especially  in  the  sternum,  are  very 
common. 

Neirvous  System. — Headache  is  one  of  the  commonest  symp- 
toms and  many  patients  complain  of  vertigo.  Neuralgia  is 
sometimes  very  annoying.  Tingling  and  formication  are  the 
commonest  paresthesias  present  in  these  cases,  and  many  of 
the  subjects  complain  of  over-sensitiveness  to  cold.  The  patel- 
lar reflex  is  diminished  in  many  cases  and  abolished  in  some 
severe  infections.  After  the  infection  has  persisted  some  time, 
neurasthenia  not  infrequently  develops  and  outbursts  of  hys- 
teria and  hystero-epilepsy  may  supervene.  Drowsiness  is 
almost  constant  except  in  mild  cases  but  insomnia  is  very  com- 


HOOK-WORM    DISEASE  47 1 

monly  met  with  and  night  terrors  are  not  rare.  Edema  of  the 
brain  sometimes  occurs  in  cases  with  a  tendency  to  anasarca. 

The  expression  is  usually  dull  and  stupid.  Lack  of  ambition 
and  intellectual  laziness  are  psychic  characteristics.  Children 
are  retarded  and  over  age  in  school.  There  is  difficulty  in 
concentration  and  delay  in  answering  questions  which  must 
ofttimes  be  repeated.  Apathy  exists  to  a  marked  degree. 
Defective  memory  is  common.  Melancholia  and  other  psy- 
choses may  develop.  Green-^*  believes  that  hook-worm  infec- 
tion is  in  many  cases  the  direct  or  indirect  cause  in  the  production 
of  a  distinct  psychiatric  entity,  the  principal  symptoms  being 
psychic  retardation,  irritability,  depression,  lackadaisicahsm 
and  blunting  of  the  higher  sensibilities. 

The  moral  perversions  dependent  on  uncinariasis  are  among 
the  most  interesting  of  the  aspects  of  the  disease.  Macdon- 
g^j(j»g269  observations  show  that  the  infection  is  responsible  for 
disobedience,  cunning,  lying,  stealing,  forgery,  and  sexual  per- 
versions, which  are  cured  by  thymol. 

Special  Senses. — Tinnitus  aurium  is  a  frequent  manifesta- 
tion. The  conjunctiva  of  the  lids  shows  anemia.  The  pupil  is 
readily  dilatable.  Stiles-"'  describes  a  symptom  which  was 
present  more  constantly  than  almost  any  other:  "If  the  patient 
is  directed  to  stare  intently  into  the  observer's  eyes  there  will 
be  noticed  a  symptom  which  is  difficult  to  describe,  but  which 
I  have  found  more  constant  than  almost  any  other  noticed, 
namely:  after  a  moment,  the  length  of  time  apparently  varying 
slightly  according  to  the  degree  of  the  disease,  the  pupils  dilate 
and  the  patient's  eyes  assume  a  dull,  blank,  almost  stupid,  fish- 
like or  cadaveric  stare,  very  similar  to  that  of  extreme  alcohoh'c 
intoxication."  This  sign  is  not  thought  by  other  observers  to 
be  pathognomonic  of  hook-worm  disease.  Blurred  vision  and 
specks  before  the  eyes  are  frequent  complaints.  Cataract  was 
common  and  corneal  ulceration  occasional  among  the  Porto 
Rico  cases.  Examination  of  the  fundus  shows  the  retina  pale, 
occasional  hemorrhages,  and  pulsation  and  convolutions  of 
veins.  Other  eye  manifestations  which  have  been  described 
are  nystagmus,  diplopia,  amblyopia,  neuritis,  asthenopia, 
restriction  of  the  visual  field,  and  chemosis  of  the  bulbo-palpe- 


472  ENDEMIC   DISEASES    OF    THE    SOUTHERN   STATES 

bral  fold.  From  observations  on  the  eye  changes,  especially 
cataract,  in  hook-worm  infections  in  the  South,  Calhoun^^"  be- 
lieves that  the  former  are  due  directly  to  the  disease,  while 
Jervey-^^  concludes  that  these  lesions  are  only  indirectly'  de- 
pendent upon  the  infection,  and  that  they  are  in  no  sense  suffi- 
ciently distinctive  or  characteristic  to  be  of  any  diagnostic 
value. 

Latent  Infections. — There  are  many  cases  of  hook-worm  in- 
festation which  cannot  be  classified  as  either  mild,  moderate, 
or  severe,  inasmuch  as  symptoms  are  entirely  absent.  Such  a 
host  is  known  as  a  "  carrier."  From  a  public-health  standpoint 
these  cases  are  the  most  important  of  all  since  they  do  not  seek 
treatment  for  their  parasites,  hence  are  difficult  to  locate. 
When  such  a  person  is  a  soil  polluter  he  may  spread  the  infection 
broadcast  without  being  suspected. 

Complications  and  Sequelae. — It  is,  of  course,  possible  that 
almost  any  disease  may  be  found  associated  with  uncinariasis. 
In  the  majority  of  instances  this  association  is  merely  a  coinci- 
dence. The  Porto  Rico  Commission-"^  record  657  complica- 
tions in  17,354  cases.  The  most  common  were  diarrhea,  dysen- 
tery, malaria  and  tuberculosis.  Other  than  intercurrent  dis- 
eases hook-worm  infection  may  bear  an  etiologic  relation  to 
gastritis,  dilatation  of  the  stomach,  enteritis,  and  dysentery.  As 
sequellse  disturbances  dependent  on  fatty  degeneration  of  the 
heart,  kidneys  and  liver  may  be  mentioned,  and  nervous  dis- 
orders have  been  attributed  as  sequelje.  Pernicious  anemia  and 
leukemia  are  supposed  to  bear  a  direct  relation  to  hook-worm 
infection  in  some  cases.  In  the  Southern  States  infestations 
with  other  intestinal  parasites  is  extremely  common  in  hook-worm 
disease.  The  commonest  worms  associated  with  hook-worms 
are  ascaris  lumbricoides,  trichiiris  trichiura,  and  hymenolepis 
nana. 


CHAPTER  XXXVn 
DIAGNOSIS  OF  HOOK-WORM  DISEASE 

While  it  is  as  easy  in  hook-worm  disease  to  examine  the  feces 
and  obtain  the  signs  of  certainty  as  it  is  to  examine  the  patient 
for  the  signs  of  probability,  it  is  as  a  rule  true  that  the  disease 
must  first  be  suspected  before  any  examinations  are  made. 
The  symptoms  which  should  cause  any  one  to  suspect  hook-worm 
disease  are  especially  anemia,  weakness,  digestive  disorders  and  a 
history  of  ground  itch.  Many  cases  come  to  the  physician  to 
be  treated  for  heart  disease  and  some  for  dropsy. 

The  following  conditions  should  invariably  lead  to  an  exami- 
nation of  the  feces :  anemia  not  due  to  malaria  or  other  obvious 
cause,  a  history  of  ground  itch,  fatigue  out  of  proportion  to 
exertion,  and  the  presence  of  eosinophilia.  In  many  instances 
the  diagnostic  clue  is  obtained  from  the  blood  examination. 
However,  it  should  be  borne  in  mind  that  the  absence  of  eosino- 
philia does  not  exclude  uncinariasis  nor  does  even  the  presence 
of  malaria  parasites. 

Too  much  stress  should  not  be  laid  upon  geophagy  as  a  diag- 
nostic sign  particularly  in  the  female  negro.  In  an  investigation 
which  I  made  upon  this  point  in  eastern  Arkansas  the  result  was 
that  of  the  female  negroes  who  came  to  me  for  troubles  other 
than  hook-worm  disease,  about  80  per  cent,  confessed  to  having 
been  dirt  or  soot  eaters. 

Occupation,  social  position  and  sanitation  of  surroundings 
may  be  taken  into  consideration  in  the  probable  diagnosis  but 
it  is  to  be  remembered  that  only  the  detection  of  the  ova  in  the 
feces  is  decisive. 

When  requesting  a  specimen  of  feces  the  physician  should 
explain  to  the  patient  that  only  a  small  quantity  is  necessary 
and  should  furnish  a  container,  otherwise  he  is  apt  to  be  brought 
an  entire  stool  in  a  large  jar  or  a  portion  of  liquid  stool  in  a 
match  box.  Small  wide-mouthed  bottles  such  as  those  for  vase- 
line and  quinine  are  suitable. 
473 


474  ■    ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

The  best  slides  for  this  purpose  are  said  to  be  the  2  by  3-inch 
slides  but  I  have  always  used  the  i  by  3 -inch.  A  drop  or  two  of 
water  should  be  placed  in  the  center  of  the  slide  and  a  quantity 
of  feces  the  size  of  a  match  head  thoroughly  mixed  to  the  proper 
consistency  and  spread  well  over  the  slide  except  for  a  narrow 
margin  along  each  edge.  A  tooth  pick  serves  the  purpose  of 
mixing  and  spreading.  A  cover-glass  should  not  be  used.  A 
i-inch  eyepiece  and  ^g-inch  objective  are  best  adapted  to  this 
work.  A  mechanical  stage  is  a  great  convenience  but  not  an  es- 
sential.    A  moderate  degree  of  illumination  is  most  appropriate. 

While  this  method  of  examination  will  certainly  detect  mod- 
erate or  severe  infections  it  is  well  known  that  even  the  most 
careful  scrutiny  of  a  single  slide  will  fail  to  detect  ova  in  many 
cases  of  light  infection.  Stiles--"  holds  that  a  negative  opinion 
cannot  be  given  until  at  least  ten  such  slides  have  been  examined, 
consuming  from  thirty  minutes  to  one  hour,  and  Dock  and  Bass-"' 
have  shown  that  in  some  cases  twenty-five  slides  may  have  to  be 
examined  before  detecting  ova.  The  time  necessary  for  this 
would,  of  course,  preclude  such  examinations  by  the  general 
practitioner,  and  as  the  importance  of  detecting  these  mild 
infections  is  of  the  greatest  degree  from  a  public-health  stand- 
point, it  becomes  necessary  to  use  some  special  method  of  con- 
centrating the  eggs  for  examination  before  pronouncing  the 
patient  free  from  infection. 

Pepper's  method  is  to  mix  the  feces  thoroughly  with  water  and 
then  centrifugalize.  The  supernatant  fluid  is  poured  off  and 
fresh  water  added,  mixed  well  and  again  centrifugalized. 
This  process  is  repeated  half  a  dozen  times  and  in  this  way  the 
bacteria,  free  coloring  matter,  light  vegetable  and  other  matter 
are  eliminated  and  only  the  ova  and  heavy  particles  remain  in 
the  bottom  of  the  tube  whence  they  may  easily  be  removed  by 
means  of  a  pipette.  Pepper  further  showed  that  ova  of  the 
hook-worm  thus  placed  on  a  slide  after  being  allowed  a  few  mo- 
ments in  which  to  settle  would  adhere  to  the  glass  when  the 
water  was  drained  off  and  would  even  withstand  the  slide  being 
rinsed  in  water.  Additional  drops  may  be  placed  on  the  slide, 
the  iJuid  drained  ofT  and  if  this  process  is  frequently  repeated 
the  glass  becomes  studded  with  ova. 


HOOK-WORM    DISEASE  475 

Bass'  method  is  a  most  valuable  one.  It  is  as  follows:  It  is 
known  that  the  specific  gravity  of  the  hookworm  egg  is  between 
1,050  and  1,100.  A  quantity  of  the  feces  is  diluted  with  about 
ten  parts  of  water  and  strained  through  gauze  to  eliminate 
coarse  matter.  This  filtrate  is  centrifugaKzed  and  the  fluid 
poured  off.  This  is  repeated  several  times  to  wash  thoroughly. 
A  fluid  of  heavy  specific  gravity  is  then  added  and  again  cen- 
trifugalized,  the  ova  remaining  in  the  top  of  the  liquid.  A  nine- 
tenths  saturated  solution  of  sodium  chloride,  or  a  solution  of 
calcium  chloride  having  a  specific  gravity  of  1,250  maybe  used 
for  this.  A  small  amount  of  the  top  fluid  is  then  poured  off 
into  a  centrifuge  tube,  water  added  and  when  centrifuged  the 
ova  go  to  the  bottom.  Dock  and  Bass-"'  state  that  without 
the  adoption  of  this  method,  of  104  cases  of  intestinal  parasite 
infection,  47  per  cent,  were  found  by  the  usual  technic  and  53 
per  cent,  were  missed  until  the  centrifuge  technic  was  employed. 
It  is  of  course  in  the  mild  infestations  that  it  is  of  such  great 
service. 

For  making  permanent  specimens  of  ova  I  have  sedimented 
them  in  2  per  cent,  formalin,  and  after  making  a  cell  of  damar 
varnish  by  means  of  the  turntable,  filled  the  cell  with  the  pre- 
servative containing  the  ova,  applied  a  circular  cover-glass 
while  the  varnish  was  still  soft  and  ringed  again  with  damar. 

Reference  to  the  chapter  on  other  intestinal  parasites  will 
assist  in  differentiating  between  hook-worm  ova  and  those  of 
other  helminths.  Besides  these  the  beginner  may  confound 
vegetable  cells  and  other  food  remnants  with  hook-worm  ova. 
A  striking  characteristic  of  the  ova  of  most  intestinal  parasites 
is  their  uniformity  and  when  once  recognized,  or  even  when 
good  plates  are  studied  there  should  be  no  difficulty  in  their 
determination. 

Attempts  to  estimate  the  number  of  parasites  from  the  num- 
ber of  ova  detected  on  examination  have  been  made.  It  is 
estimated  that  a  vigorous  female  will  lay  between  two  and  six 
thousand  eggs  in  twenty-four  hours.  Leichtenstern's-"^  method 
of  making  this  estimate  is  to  divide  the  number  of  ova  found 
in  I  gram  of  feces  by  47.  Lutz's-"^  method  is  to  make  a 
25  per  cent,  suspension  of  the  feces  in  water  and  by  a  specially 


476  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

ruled  counting-  chamber  to  estimate  the  number  of  ova  in  the 
entire  stool.  Grassi  and  Parona-"^  estimate  that  150  to  200 
ova  per  centigram  of  f eces  indicate  1,000  uncinarise,  three-fourths 
females  and  one-fourth  males.  The  Porto  Rico  Commission, ^"^ 
however,  maintain  that  no  more  shifting  ground  can  be  assumed 
than  that  one  can  judge  of  the  number  of  uncinariae  inhabiting 
an  intestine  save  in  a  general  way. 

Stiles-"^  proposed  as  a  rough  diagnostic  method  the  blotting- 
paper  test,  which  he  claims  is  useful  in  the  absence  of  a  micro- 
scope examination.  An  ounce  or  more  of  the  fresh  stool  is 
placed  on  a  piece  of  white  blotting  paper;  after  being  allowed 
to  stand  from  twenty  minutes  to  an  hour  the  stool  is  removed 
and  the  color  of  the  stain  is  examined.  A  reddish-brown  stain 
is  suggestive  of  uncinariasis.  This  test  has  not  found  wide 
favor. 

Herman-''^  endeavored  to  apply  the  method  of  serodiagnosis 
to  uncinariasis  but  the  result  of  his  experiments  was  completely 
negative. 

The  therapeutic  test  is  occasionally  advocated  as  a  diagnostic 
measure.  This  consists  of  administering  a  dose  of  anthelmintic 
and  examining  the  stool  for  worms.  Inasmuch  as  it  is  now 
readily  possible  in  most  Southern  States  to  have  feces  examined 
free  of  charge  there  is  rarely  any  justification  for  the  therapeutic 
test. 

There  are  several  diseases  from  which  uncinariasis  may  have 
to  be  diagnosticated. 

In  malaria  there  can  often  be  elicited  a  history  of  typical 
paroxysms,  splenic  enlargement  may  be  detected,  and  herpes 
is  sometimes  present.  The  blood  examination  may  show  the 
presence  of  malaria  parasites,  a  mononuclear  leucocytosis,  a 
relatively  high  color  index,  and  the  absence  of  eosinophilia. 
Malaria  is  usually  amenable  to  quinine.  The  examination  of 
the  feces  should  settle  the  diagnosis. 

In  pernicious  anemia  the  color  index  is  high,  the  blood  con- 
tains megaloblasts  as  well  as  normoblasts  and  poikilocytes. 
Eosinophilia  is  not  present.  The  skin  may  show  icterus  or 
even  pigmentation.     The  fecal  examination  is  negative. 

In  leukemia  the  blood  examination  on  one  hand  shows  an 


HOOK-WORll  DISEASE  477 

enormous  increase  in  the  leucocytes  with  the  advent  of  abnormal 
cells  together  with  splenic  enlargement,  and  on  the  other  hand 
the  examination  of  the  feces  should  render  the  diagnosis  certain. 

In  chlorosis  the  anemia  and  the  sometimes  perverted  appetite 
may  cause  temporary  uncertainty.  The  blood  examination 
and  the  color  of  the  skin  together  with  the  microscopic  examina- 
tion of  the  feces  should  clear  all  doubt. 

In  many  cases  of  uncinariasis  heart  disease  is  suspected. 
Careful  examination  of  the  heart,  however,  with  the  examina- 
tion of  the  feces  will  usually  settle  the  diagnosis. 

Bright's  disease,  tuberculosis,  syphilis  and  enteritis  may  be 
diflerentiated  from  hook-worm  disease  by  the  history,  physical 
examination  and  the  microscopic  investigation  of  the  feces. 


CHAPTER  XXXVin 
PROGNOSIS  OF  HOOK-WORM  DISEASE 

While  the  majority  of  cases  of  uncinariasis  tend  to  recover 
spontaneously  it  is  known  that  the  worms  may  live  for  years 
and  that  reinfection  is  extremely  common. 

Under  favorable  conditions  the  prognosis  of  hook-worm  dis- 
ease is  good  because  the  disease  is  usually  chronic,  affording 
time  for  diagnosis  and  treatment,  because  reinfection  is  pre- 
ventable, and  because  we  possess  a  specific  for  its  treatment. 

The  prognosis  depends  largely  on  the  severity  of  the  disease, 
the  presence  or  absence  of  complications,  and  on  the  age  of  the 
patient. 

In  the  presence  of  organic  changes  resulting  directly  from  the 
infection  and  in  the  event  of  intercurrent  diseases  the  outlook 
is  less  favorable.  The  prognosis  is  more  favorable  in  the  young 
because  the  blood-making  organs  are  commonly  more  active 
and  complications  in  vital  organs  are  less  likely  to  supervene. 

No  case  of  hook-worm  infection  should  be  treated  lightly  on 
account  of  the  depletion  of  vitality  due  directly  to  the  disease 
and  of  the  predisposition  to  and  aggravation  of  other  diseases. 

Pregnancy,  miscarriage  and  labor  are  unfavorable  complica- 
tions. 

Even  after  all  worms  are  expelled  some  cases  will  die  from  lack 
of  recuperative  power. 

Contra-indications  to  specific  treatment  render  the  prognosis 
very  grave. 

According  to  the  Porto  Rico  Commission-"^  good  resistance  to 
the  toxin  of  uncinaria  is  expressed  by  eosinophilia  and  they 
conclude : 

1.  Very  severe  chronic  cases  with  poor  resisting  power  and 
exhausted  blood-making  organs  have  little  or  no  eosinophilia. 

2.  A  rise  of  eosinophiles  is  of  good  prognostic  import. 

3.  If  very  severe  cases,  presenting  little  or  no  eosinophilia, 

478 


HOOK-WORM    DISEASE  479 

fall  in  their  eosinophile  count,  the  prognosis  is  not  generally 


The  cause  of  death  is  most  commonly  from  exhaustion,  diar- 
rhea, intercurrent  affections,  fatty  changes  in  the  heart,  kidneys 
or  liver,  or  complications  of  pregnancy  and  labor.  Intestinal 
perforation  has  been  observed  as  a  cause  of  death. 

It  is  very  difficult  to  determine  the  true  mortality  of  uncina- 
riasis for  unquestionably  many  cases  never  come  under  the 
observation  of  any  physician.  Furthermore  it  is  doubtful  if, 
as  in  the  Porto  Rico  Commission  figures  below,  all  cases  can  be 
traced  to  termination  by  cure  or  death.  The  following  figures 
show  a  mortality  of  twenty- three  hundredths  of  i  per  cent.: 

Porto  Rico  Commission'"'^ 287,568  cases,  473  deaths. 

Canal  Zone  Reports'*' 445  cases,      3  deaths. 

German  Protectorate  Reports'^'.. .        1,158  cases,  200  deaths. 

Total 289,171  cases,  676  deaths. 

Of  Sandwith's-"^  hospital  cases  89.5  per  cent,  were  cured  or 
greatly  relieved,  2.5  per  cent,  were  unrelieved,  and  8  per  cent, 
died. 


CHAPTER  XXXIX 
PROPHYLAXIS  OF  HOOK-WORM  DISEASE 

Hook-worm  disease  is  preventable.  Caused  as  it  is  by  a  para- 
site having  also  an  extracorporeal  phase  of  development  and  for 
which  there  exist  specific  remedies  it  may  be  attacked  in  both 
phases  by  several  methods. 

The  following  table  of  deaths  from  anemia  demonstrates  the 
results  obtained  through  the  campaign  of  the  Porto  Rico 
Commission-"': 

1900-01 11,875 

1901-02 6,284 

1902-03 6,830 

1903-04 6,179 

1904-0S '. 4,963 

1905-06 3,769 

1906-07 1,134 

1907-08 1,785 

The  methods  to  be  employed  against  hook-worm  disease  fall 
naturally  into  three  classes:  (i)  The  sterilization  of  carriers; 
(2)  the  prevention  of  soil  pollution;  and  (3)  the  prevention  of 
access  of  larvae,  by  mechanical  means  or  by  destruction.  For 
success  in  any  method  education  in  the  methods  of  causation 
and  prevention  is  a  sine  qua  non.  There  are  many  who  will 
follow  if  intelligently  led,  though  there  will  remain  a  few  who 
must  be  forced  even  after  they  have  been  informed  and  the 
policy  of  any  campaign  should  be  education  for  the  willing  and 
legislation  for  the  unwilling. 

I .  If  every  person  who  has  hook-worms  could  be  treated  to  a 
radical  cure  the  disease  would  be  exterminated.  Most  of  those 
seeking  medical  advice  are  so  cured  but  there  are  very  many 
who  have  the  disease  who  do  not  take  treatment,  and  there 
are  many  more  who  are  infested  but  have  no  symptoms  which 
lead  them  to  suspect  it.  These  carriers  are  a  greater  source  of 
danger  than  actual  cases  of  the  disease  for  the  latter  sooner  or 
later  are  compelled  to  take  treatment,  while  the  former  rarely 
480 


HOOK-WORM    DISEASE 


do.  It  is  impossible  to  force  hook-worm  patients  to  accept 
competent  treatment,  and  with  the  carrier  there  is  the  double 
difficulty  of  first  locating  him  and  then  sterilizing  him.  It  is, 
of  course,  the  duty  of  every  physician  treating  a  hook-worm  pa- 
tient to  explain  to  him  the  importance  of  complete  cure.  It  is, 
furthermore,  the  duty  of  physicians  to  seek  out  carriers  and  to 
educate  their  clientele  in  hook-worm  etiology  and  prophylaxis. 


Fig.  92. — An   insanitary  privy,  found   too   frequently  on   our  farms.     Notice 
how  the  animals  are  spreading  soil  pollution.     (Public  Health  Reports.) 

If  each  physician,  expecially  in  the  rural  districts,  would  con- 
stitute himself  health  officer  among  his  patients  the  hook-worm 
problem  would  solve  itself  and  the  collateral  benefits  ensuing, 
the  prevention  of  typhoid  fever  and  other  diseases,  would  be 
almost  incredible. 

As  to  guides  in  the  search  of  carriers,  residence  in  an  endemic 
area,  other  cases  in  the  family  or  neighborhood,  and  a  history  of 
ground  itch,  must  be  regarded  in  those  lacking  symptoms. 


482 


ENDEMIC   DISEASES   OF   THE    SOUTHERN   STATES 


In  industrial  concerns  it  would  be  advantageous  if  employees 
were  periodically  inspected  for  hook-worm  infection  as  is  done 
in  some  European  mines. 

2.  Since  it  is  largely  through  infected  earth  that  uncinariasis 
is  propagated  it  is  evident  that  any  scheme  of  prevention  which 
ignores  the  significance  of  soil  pollution  will  work  in  vain. 


Fig.  93. — Sanitary  privy  designed  to  prevent  soil  pollution.     Galvanized 
pails  may  be  used  instead  of  tubs.     (Public  Health  Reports.) 

Throughout  the  rural  districts  of  the  South  soil  pollution  is 
the  rule  rather  than  the  exception.  In  relatively  thickly  popu- 
lated communities  and  along  main  roads  there  is  usually  an  ex- 
cuse for  a  privy,  but  in  more  remote  districts  there  is  often  none, 
and  the  observance  of  the  hygienic  rules  against  soil  pollution 
does  not  equal  the  instinct  of  the  cat  or  the  hygienic  knowledge 
of  the  time  of  Moses. 

Only  a  very  small  percentage  of  such  privies  as  exist  prevent 


HOOK-WORM   DISEASE 


483 


to  any  degree  whatever  soil  pollution.  They  are  surface  closets, 
open  at  the  back  with  nothing  to  prevent  the  access  of  flies 
and  domestic  animals. 


<^''^'"^ticanyclo,,-njUcl_ 


^inc  lined  60, 


Fig.  94. — Mechanism  of  the  Lumsden- Roberts-Stiles  privy.     (Public 
Health  Reports.) 

There  are  five  requirements  for  a  sanitary  privy: 

1.  The  feces  must  not  lie  upon  the  ground. 

2.  Domestic  animals  must  be  excluded. 

3.  Washing  rains  must  be  guarded  against. 

4.  Flies  must  be  excluded. 

5.  The  receptacle  must  be  easily  accessible  and  capable  of 
being  cleaned. 

A  simple  and  at  the  same  time  efficient  privy  is  illustrated  in 


484  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Fig.  93.  A  small  quantity  of  earth  or  sand  in  the  bottom  of 
the  receptacle  facilitates  cleaning. 

Several  methods  of  disposing  of  night  soil  have  been  proposed ; 
heat,  chemicals,  burial,  fermentation,  etc.  While  burial  is 
perhaps  not  the  ideal  method,  it  is  reasonably  safe  if  properly 
done  and  by  far  the  most  practical  of  all.  The  excreta  should 
be  buried  at  least  18  inches  deep  and  at  least  100  yards  distant, 
and  down  hill  from  any  source  of  water  supply.  They  should 
never  be  thrown  into  any  stream  or  spread  upon  the  surface 
for  fertilizer  unless  absolutely  sterilized. 

The  Lumsden-Roberts-Stiles^^^  privy  illustrated  in  Fig.  94 
is  ideal  for  rural  homes.  The  device  consists  of  the  following 
parts: 

1.  A  water-tight  barrel  serving  as  liqueher. 

2.  A  covered  water-tight  barrel,  can  or  other  container  to  re- 
ceive the  efiiuent. 

3.  A  connecting  pipe  about  2!^  inches  in  diameter,  about  12 
inches  long,  and  provided  with  an  open  "T"  at  one  end,  both 
openings  of  the  "T"  being  covered  by  wire  screens. 

4.  A  tight  box,  preferably  zinc  lined,  which  fits  tightly  on  the 
top  of  the  liquefying  barrel ;  this  is  provided  with  an  opening  on 
the  top  for  the  seat,  which  has  an  automatically  closing  lid. 

5.  An  anti-splashing  device  consisting  of  a  small  board  placed 
horizontally  under  the  seat  and  i  inch  below  the  level  of  the 
transverse  connecting  pipe;  it  is  held  in  place  by  a  rod,  which 
passes  through  eyes  or  rings  fastened  to  the  box,  and  by  which 
the  board  is  raised  and  lowered.  The  liquefying  tank  is  filled 
with  water  up  to  the  point  where  it  begins  to  trickle  into  the 
effluent  tank. 

A  thin  film  of  oil  should  be  poured  upon  the  surface  of  the 
liquid  in  each  barrel. 

The  devisers  claim  that  the  following  requirements  are  met: 

1.  It  solves  the  fly  and  mosquito  problems  so  far  as  the  privy 
is  concerned. 

2.  It  liquefies  fecal  matter  and  reduces  its  volume  so  that  it 
may  be  safely  disposed  of  more  easily  and  cheaply  than  night 
soil. 

3.  It  reduces  odor. 


HOOK-WORM    DISEASE  485 

4.  It  reduces  the  labor  of  cleaning  the  privy  and  makes  this 
work  less  disagreeable. 

5.  It  is  of  simple  and  inexpensive  construction. 

The  location  of  the  privy  is  important.  When  inaccessible 
or  even  when  too  public  it  is  not  used.  It  should  be  placed 
within  easy  reach  of  the  house.  Proximity  encourages  its  use 
and  care. 

3.  Chemical  and  physical  means  of  destroying  ova  and  larvae 
are  not  practical,  and  in  the  European  mines  where  they  have 
been  so  thoroughly  tried  they  have  been  abandoned  in  favor  of 
the  restriction  of  soil  pollution  and  of  the  protection  of  the  feet. 

Since  it  is  known  that  the  skin  route  of  infection  is  the  usual 
one,  and  that  ground  itch  is  commonest  on  the  feet,  the  wearing 
of  shoes  in  infected  areas  has  been  shown  productive  of  good 
results.  This  means,  of  course,  the  annihilation  of  the  barefoot 
boy  immortalized  by  Whittier  and  not  a  few  artists,  but  serves 
to  translate  the  whistled  tunes,  red  lips  and  sunshiny  face  from 
the  realm  of  poetry  to  reality. 

Ashford-'^  mentions  the  case  of  a  planter  in  Porto  Rico,  em- 
ploying a  large  number  of  laborers,  who  provided  them  all  with 
shoes  at  his  own  expense  and  declared  that  he  never  made  a 
better  investment,  since  the  increase  in  efficiency  repaid  him 
many  fold.  As  this  writer  states,  the  providing  of  shoes  for 
the  poor  should  receive  the  attention  of  educationalists  and 
philanthropists. 

In  this  connection  Manson-^*  cites  an  interesting  incident: 

"A  planter  from  Trinidad,  West  Indies,  told  me  some  time 
ago  that  he  was  at  one  time  seriously  inconvenienced  by  coolie 
itch  among  his  field  hands.  He  remarked  that  the  attack  of 
coolie  itch  was  often  followed  by  profound  anemia,  and  he  also 
remarked  that  the  anemia  occurred  only  or  principally  among  the 
coolies  who  either  passed  through  or  who  worked  in  certain 
fields.  He  argued  that  in  these  fields  were  certain  germs  that, 
coming  into  contact  with  the  legs  and  feet  of  the  coolies,  pro- 
duced the  dermatitis  and,  on  subsequently  entering  the  body, 
the  specific  anemia.  He  knew  nothing  about  the  ankylostoma; 
the  observation  was  made  long  before  Looss'  discovery.  The 
planter  had  some  knowledge  of  bacteriology  and  he,  like  many 


4»6  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Others,  thought  that  the  germ  in  question  was  a  bacterium,  and 
that  by  some  antiseptic  and  protective  procedure  he  could  either 
kill  the  germ  or  prevent  its  access  to  the  skin.  In  casting  about 
for  a  means  to  effect  this  he  bethought  him  of  a  practice  he  had 
seen  in  operation  in  a  certain  part  of- Germany  during  one  of  the 
annual  pilgrimages  he  made  to  that  country  in  search  of  health. 
In  that  particular  part  of  Germany  geese  are  raised  in  large 
numbers.  The  goose  market  is  a  long  way  from  many  of  the 
goose  farms,  so  that  the  birds,  when  ready  for  sale,  have  to  be 
delivered  for  many  miles  over  the  hard  roads.  To  enable  their 
feet  to  stand  the  journey  the  farmer  provides  each  of  his  birds 
with  a  pair  of  close-fitting  socks  and  sandals.  This  he  fits  on  in 
this  wise :  He  fills  a  shallow  trough  with  tar  and  through  this 
trough  he  drives  the  geese  onto  a  piece  of  ground  covered  with 
fine  sand.  The  tar  sticks  to  their  feet  and  the  sand  to  the  tar; 
the  birds  are  shod  for  the  road.  Thus  provided  they  perform 
the  long  journey  without  injury.  Acting  on  this  hint  the  planter 
made  his  coolies,  on  their  way  to  their  work  in  the  morning,  dip 
their  feet  and  legs  in  a  bucket  of  Barbadoes  tar  and  then  walk 
across  a  layer  of  sawdust  or  sand.  The  result  was  excellent. 
Coolie  itch  and  coolie  anemia  almost  disappeared  from  the 
plantation." 

Children  should  constantly  be  drilled  to  keep  the  fingers  out 
of  their  mouths.  It  is  impossible  to  keep  their  hands  clean,  and 
diseases  other  than  hook-worm  are  frequently  conveyed  in  this 
manner.  Those  who  till  the  soil  or  handle  the  products  of  the 
soil  should  be  taught  to  wash  the  hands  frequently. 

In  many  European  mines  shower  baths  have  been  installed 
for  the  miners. 

Bathing  in  common  tubs  by  those  exposed  to  hook-worm 
infection  is  conducive  to  the  spread  of  the  disease. 

After  all  is  said  and  done  in  the  prophylaxis  of  uncinariasis  the 
results  will  not  be  proportionate  to  the  efforts  until  a  popular 
demand  for  sanitation  is  created  throughout  the  rural  districts. 
This  must  be  accomplished  through  a  campaign  of  education 
beginning  with  the  children.  The  Rockefeller  Sanitary  Com- 
mission has,  in  a  few  years,  come  nearer  this  end  than  all  other 
combined  agencies  throughout  the  past. 


CHAPTER  XL 
TREATMENT  OF  HOOK-WORM  DISEASE 

Hook-worm  disease  is  a  curable  affection,  there  being  one  or 
more  specifics  for  its  relief.  It  is  true  that  patients  die  of  hook- 
worm infection  even  under  treatment,  but  if  appropriate  treat- 
ment is  begun  reasonably  early  and  persisted  in  practically  all 
these  cases'  recover  promptly. 

The  most  efficient  remedy  for  uncinariasis  is  thymol,  first  used 
for  this  disease  by  Bozzolo'^''  in  1879.  Thymol  consists  of  large 
colorless,  translucent,  hexagonal  crystals,  with  an  aromatic 
odor  and  pungent  taste.  It  is  obtained  from  the  volatile  oils 
of  thymus  vulgaris,  thymus  monarda  and  carum  ajowan.  It  is 
soluble  in  1,100  parts  of  water,  and  in  less  than  one  part  of  alcohol, 
ether  or  chloroform,  it  is  readily  soluble  in  glacial  acetic  acid, 
carbon  disulphide  and  in  fixed  and  volatile  oils.  It  liquefies 
when  triturated  with  equal  quantities  of  camphor,  menthol  or 
chloral.     When  liquefied  by  fusion  it  is  lighter  than  water. 

Thymol  has  poisonous  properties,  but  in  proper  dosage  ad- 
ministered with  due  precautions,  it  is  a  very  safe  drug.  It  is 
neither  uncertain  nor  unreliable,  and  so  far  as  I  am  aware  espe- 
cial idiosyncrasies  toward  it  are  not  common.  It  is  a  powerful 
antiseptic,  said  to  be  ten  times  less  toxic  than  carboKc  acid; 
indeed  it  is  not  unhke  the  latter  in  some  of  its  systemic  effects 
as  well  as  in  chemical  nature. 

The  commonest  symptoms  following  thymol  administration 
are  nausea,  depression,  burning  in  the  epigastric  region  and 
vertigo.  It  is  ehminated  principally  by  the  lungs  and  kidneys, 
and  the  urine  may  become  very  dark  and  increased  in  quantity. 
These  symptoms  are  usually  aggravated  by  getting  out  of  bed. 
Everything  possible  should  be  done  to  prevent  the  absorption 
of  the  drug,  as  it  is  not  the  patient  that  is  to  be  treated  but 
the  worms,  and  the  more  of  the  medicine  absorbed  by  the  host 
the  less  his  parasites  receive.  When  absorbed,  nausea  and  vom- 
487 


400  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

iting,  diarrhea  and  tremors  may  occur.  The  temperature  is 
frequently  lowered,  the  pulse  may  be  rapid  and  weak  and  dysp- 
nea and  cyanosis  may  develop.  Profuse  sweating  and  collapse 
have  been  observed,  and  convulsions  and  delirium  may  ensue. 
The  drug  is  said  to  irritate  the  kidneys  in  some  cases.  The 
heart  symptoms  are  due  to  the  effect  of  the  thymol  on  the  heart 
muscle  and  to  the  lowered  blood  pressure. 

Stiles  and  Boatwright-^^  have  recently  studied  the  subjective 
effects  in  464  administrations  of  thymol  to  243  patients.  The 
results  of  their  observations  are  recorded  in  the  following 
tabulation : 


Total  treatments 

Ill  effect  absent 

Ill  effect  present  (as  follows) 

Sickness  at  the  stomach 

Weakness 

Burning  in  the  stomach 

Dizziness  (including  also  "giddiness,"  "drunk"  "staggery' 

Headache 

Vomiting 

Burning  in  throat 

Pain  in  stomach 

Drowsiness  or  sleepiness 

Sick  after  discharge  from  treatment 

Chill  apparently  not  due  to  treatment 

Dyspnea 

Irregular  heart  following  thymol 

Fainted 

Deaths 


464 
259 
205 
66 
62 
4S 


100. 

55- 


0.64 


Stiles  and  Leonard"^  state  that  they  know  of  at  least  eleven 
deaths  in  this  country,  due,  so  far  as  it  has  been  possible  to 
determine,  either  to  following  thymol  with  castor  oil  instead  of 
with  salts,  or  to  carelessness  in  respect  to  following  out  the  usu- 
ally adopted  procedure. 

Bozzolo,^^'  ThornhilP^  and  others  report  cases  of  fatal  poison- 
ing by  thymol. 

Thymol  poisoning  should  be  treated  systematically.     Mor- 


HOOK-WORM    DISEASE  4S9 

phine  and  atropin  are  usually  indicated,  and  digitalis,  ergot  or 
strychnine  may  be  needed.  Hot  coffee  should  be  avoided  as  it 
is  a  solvent  of  the  drug.     External  warmth  is  not  to  be  used. 

Thymol  is  contra-indicated  in  great  debility,  advanced  old 
age,  organic  heart  disease,  nephritis,  gastritis,  dysentery,  and 
pregnancy.  In  some  such  cases,  however,  it  may  be  deemed 
safer  to  administer  the  drug  than  to  withhold  it.  The  Porto 
Rico  Commission  sometimes  treated  pregnant  women  with 
thymol  to  save  Kfe,  and  on  several  occasions  nursing  mothers 
were  given  the  drug  without  bad  effect  to  either  mother  or  child. 

The  American  school  is  inclined  to  regard  with  disfavor  the 
large  doses  of  thymol,  even  up  to  120  grains,  advocated  by  the 
Europeans.  In  gauging  the  dose  of  thymol  the  apparent  age, 
real  weight  and  degree  of  debility  should  be  the  determining 
factors  rather  than  the  real  age.  There  are  few  diseases  in 
which  the  real  and  apparent  ages  have  such  a  wide  degree  of 
variation  and  the  latter  must  be  taken  into  consideration. 
Subjects  with  contra-indications  to  thymol  should,  if  treated, 
be  given  small  doses  and  repeated;  they  should  be  "fractionally 
sterilized."  The  following  scale  of  dosage  is  recommended  by 
Ashford  and  King,  and  widely  used  in  the  Southern  States: 

Under  5  years  old,  in  size 7}^  grains. 

S  to  10  years  old,  in  size 15  grains. 

10  to  IS  years  old,  in  size 30  grains. 

15  to  20  years  old,  in  size 45  grains. 

20  to  60  years  old 60  grains. 

Over  60  years  old 30  to  45  grains. 

The  parasites  lie  in  the  small  intestine,  many  of  them  with 
head  and  neck  imbedded  in  the  mucosa.  They  are  covered 
with  the  normal  mucus  of  the  gut,  together  with  that  produced 
by  mechanical  irritation.  In  addition  the  food  contents  of  the 
bowel  envelops  the  worms.  It  can  be  seen  that  under  these 
circumstances  a  dose  of  anthelmintic  might  kill  none  and  sicken 
and  dislodge  only  a  few  parasites.  Hence  it  becomes  imperative 
to  prepare  the  intestine  for  the  medicine.  The  patient  should 
eat  sparingly  the  day  before  treatment  and  take  only  liquids  for 
the  evening  meal.  At  bedtime  a  purge  should  be  administered. 
Sulphate  of  soda  and  the  sulphate  of  magnesia  are  the  most 


490  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

suitable ;  the  former  especially  seems  to  liquefy  and  remove  the 
protecting  mucus.  On  the  day  of  treatment  the  patient  should 
remain  in  bed  and  should  not  be  allgwed  any  nourishment  until 
through  with  the  treatment.  Especially  should  no  milk,  butter, 
other  oils  or  fat,  alcohol,  turpentine,  ether  or  chloroform  be 
permitted,  as  these  are  solvents  of  thymol.  The  thymol  should 
be  thoroughly  triturated  with  an  equal  quantity  of  sugar  of 
milk  to  prevent  packing.  It  may  be  given  in  capsules  or  in 
cachets.  To  children  who  cannot  swallow  these  it  is  usually 
given  suspended  in  syrup  or  mucilage  of  acacia.  The  dose 
selected  is  ordinarily  divided  into  two  parts  and  administered 
two  hours  apart,  say  at  8  a.m.  and  at  lo  a.m.  At  noon  another 
dose  of  the  saline  is  given  and  in  an  hour  the  patient  may  be 
allowed  nourishment,  excluding  rigidly  the  solvents  of  the  drug. 
The  directions  to  the  patient  should  be  given  in  the  minutest 
detail,  and  should  be  reduced  to  writing.  The  patient  should  be 
instructed  to  save  the  stool  for  inspection.  He  should  not  be 
obliged  to  walk  to  a  privy  or  water  closet,  but  should  use  a  bed 
pan  or  vessel  at  the  edge  of  the  bed.  As  Stiles  suggests,  Sun- 
day is  a  convenient  day  for  treating  working  people  and  school 
children. 

Although  thymol  is  a  specific  for  hook-worm  disease,  this  does 
not  mean  that  cures  are  always  accomplished  by  a  single  dose,  a 
Iherapia  sterilisans  magna.  On  the  other  hand,  while  at  least 
three-fourths  of  the  parasites  are  expelled  at  the  first  treatment, 
usually  several  repetitions  are  necessary  to  effect  a  radical  cure. 
In  many  cases  a  single  dose  expels  so  many  worms  that  the 
patient  is  greatly  improved  clinically,  but  is  not  sterilized  and 
remains  a  carrier  to  infect  others.  Sandwith^"^  found  that  an 
average  of  2.6  treatments  were  necessary  to  cure  hospital  cases. 
His  observations  on  184  cases  are  as  follows: 

One  dose  cured 42  patients. 

Two  doses  cured 58  patients. 

Three  doses  cured 42  patients. 

Four  doses  cured 25  patients. 

Five  doses  cured g  patients. 

Six  doses  cured 4  patients. 

Seven  doses  cured 2  patients. 

Eight  doses  cured 2  patients. 


HOOK-WORM    DISEASE  49I 

Ashford,  King  and  Igaravidez-"-  recorded  in  3,630  patients 
the  number  of  treatments  necessary  to  effect  a  complete  cure, 
averaging  2.04  doses  per  patient: 


Number  of  doses 

Number  of  patients 

Number  of  doses 

Numbe: 

r  of  patients 

I 

i,5iS 

7 

19 

2 

1,166 

8 

6 

3 

S18 

9 

3 

4 

247 

10 

I 

5 

104 

II 

I 

6 

47 

While  most  authorities  recommend  at  least  three  doses  for 
all  patients  as  routine,  I  am  of  the  opinion,  inasmuch  as  many 
patients  are  radically  cured  by  one  dose,  that  repetitions  after 
the  first  dose  be  based  solely  upon  microscopic  evidence  of 
more  parasites  in  the  intestines.  These  examinations  should 
be  made  at  weekly  intervals  and  should  be  repeated  at  least 
three  times,  because  a  dose  of  thymol  which  may  not  destroy  all 
worms  may  suspend  ovulation  for  a  week  or  two.  Weekly 
intervals  are  the  most  suitable  intervals  also  for  the  repetition 
of  treatment  should  it  be  necessary. 

To  recover  the  parasites  from  the  stools  I  have  found  useful 
a  large  flat  baking  pan, known  in  the  South  as  the  "biscuit  pan. " 
This  should  be  painted  black  and  In  one  end  about  an  inch  from 
the  bottom  should  be  punctured  a  row  of  small  holes  so  that 
the  diluted  feces  may  be  retained  or  released  by  tilting  without 
agitating.  Straining  through  gauze  is  also  a  very  satisfactory 
method. 

After  treatment  patients  usually  begin  to  show  unmistakable 
evidence  of  improvement  in  from  three  to  five  days.  Improve- 
ment depends  largely  upon  the  intensity  of  the  infection  and 
the  resistance  of  the  patient,  considered  under  Prognosis. 

In  certain  cases  thymol  does  not  give  the  good  results 
anticipated.  In  some  of  these  it  is  because  the  alimentary 
canal  has  not  been  properly  prepared  and  the  drug  does  not 
gain  access  to  all  the  parasites.  In  other  cases  the  thymol  be- 
comes lumped  in  the  alimentary  canal  and  passes  through  like  a 
marble.  There  remains  a  small  group  of  cases  in  which  the  only 
explanation  seems  to  be  that  the  worms  are  of  a  thymol-resistant 


492 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


strain.  Analogies  are  found  in  other  parasitic  diseases,  notably 
the  quinine-fast  parasites  in  certain  resistant  cases  of  malaria. 
Of  other  drugs  for  the  specific  treatment  of  uncinariasis 
heta-naphthol  introduced  by  Bentley"'  in  1904  is  the  most  serv- 
iceable. Bentley  used  it  in  several  thousand  cases  with  ex- 
cellent results  and  prefers  it  to  thymol.  It  is  used  in  half  the 
dose  of  thymol  and  is  very  much  cheaper.  It  is  less  depressing 
than  thymol  but  more  irritating  to  the  kidneys,  a  serious  draw- 
back in  view  of  the  frequency  of  albiminuria  in  the  disease. 
The  treatment  preparatory  to  beta-naphthol  is  the  same  as  that 
for  thymol.  The  Porto  Rico  Commission-"^  made  a  compara- 
tive study  of  the  value  of  thymol  and  of  beta-naphthol  as  shown 
by  the  percentage  of  the  total  number  of  parasites  expelled  by 
successive  doses  of  each  drug.  Their  observations  may  be  sum- 
marized as  follows : 


Doses 

Thymol 

Beta-naphthol 

One 

Two                 

76.84  + 
92-39  + 
97-56  + 
99-07  + 
99-80+ 

72.24  + 
88.13  + 

Three                    

93.68  + 

Four 

Five 

98.75  + 

This  shows  that  thymol  is  somewhat  more  efl&cient  than  beta- 
naphthol  in  the  treatment  of  uncinariasis.  Even  a  slight  degree 
of  difference  is  important  in  the  prevention  of  carriers  as  a  result 
of  lack  of  complete  cure. 

Male  Jem  has  been  used  largely  and  successfully  in  Europe 
for  the  treatment  of  infection  with  the  old-world  hook-worm,  but 
seems  to  be  relatively  inert  against  the  new-world  species. 

Herman's  mixture,  consisting  of  chloroform  3  grams,  oil  of 
eucalyptus  2  grams,  and  castor  oil  40  grams,  to  be  given  in  two 
divided  doses  an  hour  apart,  has  been  used  successfully  and 
has  the  advantage  for  research  purposes  of  expelling  the  worms 
alive.  It  is  said  to  be  a  nauseous  dose  and  will  hardly  supplant 
thymol  in  popularity. 

Oil  of  chenopodium  has  recently  come  into  repute  as  a  remedy 
for  hook-worm  disease.     Liquid  diet  and  a  saline  should  be  used 


HOOK-WORM   DISEASE  493 

preparatory  to  the  drug.  The  next  morning  three  doses  of  the 
oil  are  given  at  two  hourly  intervals.  The  following  individual 
doses  have  been  recommended: 

From    6  to  8  years 8  drops. 

From    9  to  10  years 10  drops. 

From  ii  to  16  years 12  drops. 

Over  16  years 12  to  16  drops. 

It  is  not  disagreeable  to  take,  is  not  accompanied  by  unpleas- 
ant symptoms  and  is  said  to  be  very  effective. 

The  number  of  other  drugs  advocated  for  the  specific  treat- 
ment is  almost  legion,  but  none  possess  any  particular  virtues. 

Archibald  has  recently  suggested  an  autogenous  vaccine  pre- 
pared from  bacteria  of  the  colon  group  on  the  theory  that  the 
intoxication  is  largely  due  to  the  absorption  of  the  to.xins  of 
these  germs. 

Uncomplicated  ground  itch  is  not  often  seen  by  the  physician, 
but  secondary  infection  may  cause  the  patient  to  seek  medical 
aid.  Pustules  should  be  opened,  crusts  removed  and  the  parts 
soaked  in  a  hot  antiseptic  solution  and  then  dressed  with  wet 
antiseptic  dressings. 

The  treatment  of  uncinaria  infection  before  ova  have  ap- 
peared in  the  stools  is  futile  inasmuch  as  the  encysted  larvce 
are  very  resistant  to  treatment. 

The  majority  of  patients  should  receive  aid  to  the  blood- 
making  organs  to  restore  the  lost  blood.  Proper  hygiene,  air, 
sunshine  and  nutritious  food  are  of  prime  importance.  Iron 
is  usually  indicated,  and  the  preferable  forms  are  Blaud's  pills 
and  the  peptonate  of  iron  and  manganese. 


CHAPTER  XLI 
OTHER  INTESTINAL  PARASITES 

It  is  probable  that  the  pathogenic  importance  of  intestinal 
parasites  other  than  hook-worm  and  the  dysenteric  ameba  has 
been  as  frequently  under-  as  over-estimated.  There  is  a  marked 
tendency  on  the  part  of  the  laity  to  magnify  the  importance  of 
these  worms,  and  all  the  symptoms  in  the  category  of  disease 
have  been  attributed  to  them.  On  the  other  hand,  most  physi- 
cians who  have  not  paid  particular  attention  to  this  branch  of 
the  pathology  of  our  Southern  States  are  apt  to  minimize  their 
significance  and  regard  them  as  innocent  commensals  of  their 
host. 

The  numerous  cases  of  mechanical  injury  caused  by  intestinal 
parasites,  as  in  obstruction  and  appendicitis,  as  well  as  the  many 
instances  in  which  toxins  have  provoked  trouble,  forces  on  us 
the  realization  that  they  are  potential  factors  for  evil. 

Every  child  infested  with  intestinal  worms  is  more  or  less 
handicapped  and  most  adult  hosts  are  at  least  less  eifiicient. 
Something  of  the  bearing  these  parasites  have  on  the  predis- 
position to,  and  aggravation  of  other  diseases,  may  be  gathered 
from  the  fact  that  after  quarantining  the  prisoners  in  Bilibid 
prison  who  were  entertaining  intestinal  worms  the  death  rate 
fell  from  75  per  1,000  to  9  per  1,000.-"'^ 


Stiles  and  Garrison 

Canal  Zone 

Hook-worm 

Ascaris  lumbricoides 

6,219 

3-792 

2,846 

19 

1,503 

95 

62 

39 

15,137 
6,359 

Hymenolepis  nana 

Oxyuris  vermicularis 

Tffinia  saginata 

Strongyloides  intestinalis 

9 

26 

53 

3,149 

97 

250 

I 

496 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


The  different  helminths  occur  with  great  variation  in  fre- 
quency in  different  localities.  In  the  foregoing  tabulation  the 
first  column  is  the  result  of  a  compilation  by  Stiles  and  Garrison-^* 
of  results  by  observers  in  many  parts  of  the  world.  The  second 
column  shows  the  finding  of  the  laboratories  of  the  Canal  Zone 
as  recorded  in  the  reports  from  1907  to  1913. 

Since  the  inauguration  of  the  work  of  the  Rockefeller  Sani- 
tary Commission  the  relative  frequency  of  the  various  parasites 
of  the  Southern  States  is  determinable,  and  the  magnitude  of 
their  figures  probably  eliminates  any  large  degree  of  error. 
Below  are  given  the  results  of  the  work  of  this  commission  as 
well  as  of  other  investigators. 


Stiles  and 

Garrison 

(214) 

Kohl- 
heim 
(2S7) 

Rockefeller 

Sanitary  Com., 

1911-1913 

Rockefeller 

Sanitary  Com., 

2nd  qtr.  1914 

(258) 

Total 

Hook-worm 

Ascaris  lumbricoides...  . 

Trichuris  trichiura 

Hymenolepis  nana 

Oxyuris  vermicularis .  .  . 

Taenia  saginata 

Strongyloides      intesti- 

36 

17 

266 

12 

45 
2 

■     8 

269 
21 

17 
15 

5 

29,743 

18,820 

5,757 

1,879 

177 

102 

S3 
3 

56,543 

25,873 

8,330 

2,424 

806 

581 

23 

23 

55,941 

27,188 

8,447 

2,714 

818 

125 

89 
3 

95,325 

Total 

386 

327 

31,588 

From  the  beginning  of  the  work  of  the  commission  in  Arkan- 
sas to  June  30,  1914,  the  following  results  were  obtained :-°' 

Number  persons  examined 43,528 

Infected  with  hook-worm 9,434 


Ascaris 

Hymenolepis. . 

Trichuris 

O.^yuris 

T.  saginata. . . 
Strongyloides . 
Cercomonas. . 
Flv  larvse. .  .  . 


138 

193 

13 

34 

16 


Mixed  infections  are  common.     The  combinations  do  not 
seem  to  depend  on  any  particular  affinities  or  elements  of  sym- 


OTHER  INTESTINAL  PARASITES  497 

biosis  but  are  in  direct  ratio  to  the  frequency  of  single  infections 
by  the  particular  species  concerned. 

Negroes  are  much  more  susceptible  to  infection  than  are  the 
whites.  Indians  are  said  to  be  infrequently  the  hosts  of  hel- 
minths.^*" 

Females  are  more  frequently  infested  than  males. 

Children  entertain  most  varieties  of  intestinal  worms  much 
more  frequently  than  adults. 

While  the  inhabitants  of  cities  are  not  immune  to  the  inva- 
sion of  parasites,  they  are  much  less  frequently  infested  than 
residents  of  rural  districts. 

The  diagnosis  of  intestinal  helminthiasis  rests  solely  on  the 
discovery  in  the  feces  of  worms  or  their  segments  or  ova. 

The  determination  of  the  various  ova  is  among  the  simplest 
of  microscopic  procedures  and  with  a  little  experience  should 
sufJBice  to  enable  one  to  make  an  accurate  diagnosis.  A  small 
bit  of  fecal  matter  the  size  of  a  match  head  should  be  rubbed  on 
a  glass  sHde  with  sufficient  water  to  spread  it  well  and  examined 
with  a  2^-inch  objective. 

TMmA  SAGINATA 

The  beef  tapeworm,  the  fat  tapeworm,  T.  mediocanellata, 
T.  inermis. 

While  the  tapeworms  have  been  known  from  the  earliest  times, 


Fig.  95. — Ovum  of  tenia  saginata,  enlarged. 

it  was  Kuchenmeister,  in  1852,  who  first  distinguished  between 
the  unarmed  Tania  saginata  and  the  armed  Tmnia  solium. 

The  geographic  distribution  of  the  parasite  comprises  all 
continents  and  in  most  localities  is  the  commonest  of  the  larger 
cestodes  infesting  man.     In  Abyssinia  infestation  is  said  to  be 


498  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

well-nigh  universal  owing  to  the  prevailing  practice  of  eating 
uncooked  beef.  In  the  United  States  Tania  saginata  is  far  com- 
moner than  Tania  solium  but  rarer  than  the  dwarf  tapeworm. 
Of  56,543  cases  of  intestinal  parasites  recorded  by  the  Rocke- 
feller Sanitary  Commission  there  were  102  of  Tcenia  saginata. 

It  is  stated  that  this  tapeworm  is  found  in  Jews  far  oftener 
than  is  the  pork  tapeworm.     The  negro  is  not  immune. 

In  my  experience  males  are  more  often  infested  than  females. 
Stiles  and  Garrison-"  found  infestation  in  females  more  than 
twice  as  prevalent  as  in  males.  Of  Hosier  and  Peiper's-"  cases 
there  were  eighty-eight  men  and  twenty-four  women. 

The  age  of  most  hosts  is  from  twenty  to  forty-five  years, 


Fig.  96. — Scolex  of  tenia  saginata,  enlarged. 

though  no  age  can  be  said  to  be  exempt.  My  youngest  patient 
was  nine  years  old  and  he  had  then  harbored  the  worm  for  sev- 
eral years.  Schloss^^^  reports  five  cases  in  children  from  six  to 
twelve  years  of  age. 

The  beef  tapeworm  in  the  adult  state  is  found  only  in  man. 
Cattle  serve  as  intermediate  hosts  for  the  larvae  which  are 
imbedded  in  the  tongue  and  other  muscles. 

The  source  of  infection  in  man  is  the  eating  of  raw  or  insuffi- 
ciently cooked  "measly"  beef,  that  is,  beef  infected  with  the 
cysticercus  bovis,  or  larvffi  of  Tcsnia  saginata. 

The  beef  tapeworm  is  usually  from  12  to  30  feet  in  length,  but 
specimens  up  to  36  and  even  74  meters  long  are  recorded. 


OTHER  INTESTINAL  PARASITES 


499 


The  proglottides  average  from  i,ooo  to  1,300111  number.  The 
head  is  subcubical  and  from  1.5  to  2  mm.  in  diameter.  There 
are  no  booklets.  The  suckers  are  circular  and  about  0.8  mm. 
in  diameter.  The  rostellum  is  rudimentary  being  replaced  by  a 
sucker-like  organ.  The  neck  is  long  and  narrower  than  the  head. 
The  proglottides  gradually  increase  in  size,  when  sexually  ma- 
ture measuring  4  to  6  mm.  long  by  8  to  10  mm.  broad.  Gravid 
segments  measure  12  to  20  mm.  long  by  4  to  7  broad.  The 
uterus  has  from  20  to  35  dichotomous  branches  on  each  side  of 
and  shorter  than  the  median  trunk. 

The  eggs  are  subglobular  and  if  the  shell  remains  intact  one 
or  two  filaments  are  found.    The  six-hooked  embryo  is  surrounded 


Fig.  97. — Segments  of  tenia  saginata,  natural  size. 

by  a  radially  striated  capsule.  The  ova  are  transparent  or 
bile  stained  and  measure  30  to  40  microns  by  20  to  30  microns. 

Abnormalities  in  the  morphology  of  this  parasite  are  not  rare 
and  monstrosities  of  scolex  and  proglottides  are  reported. 

Symptoms. — The  majority  of  persons  infested  with  the  beef 
tapeworm  do  not  complain  of  symptoms,  at  least  until  after 
they  discover  the  presence  of  the  parasites.  When  symptoms 
are  present  there  is  nothing  characteristic  about  them.  The  old 
idea  that  tapeworm  patients  have  enormous  appetites  is  in  a 
measure  erroneous.  The  appetite  is  capricious  in  many  cases 
and  anorexia  or  buhmia  occur  in  a  few.  Dyspeptic  symptoms, 
increased  flow  of  saliva,  belching  and  nausea  are  complained  of 
in  some  cases.  Colickypains  in  the  epigastrium  orhypogastrium 
are  sometimes  felt.  Constipation  may  be  present  and  diarrhea 
is  an  occasional  symptom.  Nervousness  may  be  marked, 
especially  in  young  patients.     Poor  and  disturbed  sleep  are  not 


500  ENDEMIC   DISEASES    OF   THE    SOUTHERN    STATES 

infrequent.  Vertigo,  tinnitus,  palpitation,  anal  and  nasal  pru- 
ritus, and  malaise  sometimes  appear.  Syncope,  convulsions 
and  visual  disturbances  are  rare  symptoms.  Some  patients 
complain  of  being  conscious  of  the  movement  of  the  worm. 
Segments  may  be  passed  in  defecation  or  may  escape  spontane- 
ously and  may  be  found  in  the  clothing  or  bedding  or  about  the 
room. 

The  blood  examination  usually  shows  an  increase  in  the  eosino- 
philes  and  the  feces  may  contain  Charcot-Leyden  crystals. 

It  is  not  known  how  long  the  beef  tapeworm  may  live  in  the 
intestines  but  since  certain  of  the  cestodes  may  hve  as  long 
as  thirty-five  years  it  is  probable  that  taenia  saginata  may 
survive  a  number  of  years.  From  the  time  of  swallowing 
the  cysticercus  until  segments  appear  in  the  stools  is  about 
sixty  days.  The  average  daily  growth  of  the  parasite  is  said 
to  be  7  cm. 

Infection  with  a  single  parasite  is  the  rule  but  as  many  as  fifty- 
nine  are  recorded  in  one  patient.^^^ 

The  diagnosis  can  be  made  only  by  the  passage  of  segments  or 
the  finding  of  ova  in  the  feces. 

The  differentiation  between  taenia  saginata  and  t^nia  solium 
may  be  made  by  examination  of  the  scolex  or  of  mature  pro- 
glottides. If  the  scolex  is  armed  with  hooks  the  specimen  is 
taenia  solium.  Proglottides  should  be  examined  pressed  be- 
tween glass  slides.  In  the  beef  tapeworm  the  lateral  uterine 
branches  number  from  twenty  to  thirty-five,  while  in  the  pork 
tapeworm  they  are  usually  less  than  fifteen. 

The  prognosis  is  favorable  but  the  beef  tapeworm,  of  all  the 
cestodes,  being  the  most  resistant  to  anthelmintics,  several 
treatments  may  be  necessary  before  the  scolex  is  removed. 

The  prophylactic  measures  consist  of  the  prevention  of  soil 
pollution,  and  efficient  system  of  meat  inspection,  cold  storage 
for  three  weeks,  or  thorough  cooking  of  beef. 

In  the  treatment  of  tapeworm  infection  the  preparatory  treat- 
ment is  of  scarcely  less  importance  than  the  specific  medication. 
Directions  to  the  patient  should  be  minutely  detailed  and  re- 
duced to  writing. 

The  patient  should  subsist  upon  liquids  only  during  the  entire 


OTHER    INTESTINAL    PARASITES  50I 

day  preceding  the  administration  of  the  specific.  At  bedtime 
half  an  ounce  of  magnesium  sulphate  is  given.  The  next  morn- 
ing no  breakfast  is  allowed  and  the  anthelmintic  is  given  on  an 
empty  stomach. 

The  best  remedy  against  the  beef  tapeworm  is  a  fresh  prepa- 
ration of  the  oleoresin  of  male-fern.  An  average  dose  is  i 
dram.  In  children  from  five  to  ten  years  old  I  have  given  from 
twenty  to  thirty  drops.  It  may  conveniently  be  administered 
in  several  large  capsules.  The  parasite  is  not  killed  by  anthel- 
mintics, but  merely  stupefied  and  it  must  be  removed  by  a 
purgative.  Two  hours  after  giving  the  male-fern  is  the  proper 
interval  and  the  sulphate  or  citrate  of  magnesia  are  suitable. 
Castor  oil  should  not  be  used  for  this  purpose. 

Pomegranate  is  an  efficient  taeniafuge  in  many  cases.  It 
should  be  used  in  the  form  of  the  fluid  extract,  dose  half  a  dram. 
Pelletierin  is  a  mixture  of  the  alkaloids  of  pomegranate.  An 
average  dose  is  lo  grains.  This  as  well  as  all  other  anthelmin- 
tics should  be  preceded  and  followed  by  brisk  purgatives. 

Pumpkin  seed  is  a  safe  and  fairly  efficient  remedy.  One  or 
2  ounces  of  the  ground  seeds  should  be  given  in  sugar  and 
water.  Cusso,  kamala  and  turpentine  are  rarely  used  at  the 
present  day. 

As  the  worm  is  about  to  be  passed  the  patient  should  be  seated 
on  a  vessel  containing  warm  water  over  which  gauze  or  coarse 
cloth  is  suspended  to  receive  the  parasite.  Care  should  be 
taken  to  avoid  breaking  the  worm  and  no  traction  should  be 
made.  If  the  bowels  cease  to  move  before  expulsion  is  complete 
an  enema  of  warm  water  should  be  given. 

Search  should  be  made  for  the  head.  On  account  of  its  small 
size,  however,  failure  to  find  it  does  not  necessarily  indicate  that 
it  has  not  been  passed.  In  the  latter  event  proglottides  will 
reappear  in  the  feces  within  three  months. 

T./ENIA  SOLIUM 

The  pork  tapeworm,  the  armed  tapeworm. 

While  Tania  solium  is  almost  cosmopolitan  and  in  certain 
locahties  the  commonest  cestode,  it  is  far  rarer  in  the  South  than 
either  the  beef  tapeworm  or  the  dwarf  tapeworm.     There  are 


502  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

no  cases  of  this  parasite  recorded  in  the  reports  of  the  Rocke- 
feller Sanitary  Commission. 

In  the  adult  stage  this  parasite  inhabits  the  small  intestine 
of  man  only.  In  the  cysticercal  or  larval  stage  the  common  host 
is  the  domestic  swine,  but  it  is  known  also  in  the  wild  boar,  man. 


Fig.  98. — Scolex  of  tenia  solium,  enlarged. 

certain  species  of  monkeys,  bears,  the  dog,  rat,  sheep,  cat  and 
deer. 

The  mode  of  infection  in  man  is  eating  pork  infested  with  the 
larvae  of  the  pork  tapeworm. 


a  b 

Fig.  99. — Ripe  proglottides  of  a,  tenia  solium  and  b,  tenia  saginata. 

Tcenia  solium  does  not  attain  the  length  of  saginata,  averaging 
from  6  to  10  feet  and  consisting  of  800  or  900  segments.  The 
scolex  is  subglobular,  0.6  to  i  mm.  in  diameter.     The  short, 


OTHER    INTESTINAL    PARASITES  503 

thick  rostellum  is  armed  with  a  double  wreath  of  hooks,  22  to 
32  in  number,  oftenest  26  or  28.  The  4  circular  suckers  are 
0.4  to  0.5  mm.  in  diameter.  The  neck  is  slender.  The  pro- 
glottides increase  gradually  in  size,  mature  ones  measuring  10  to 
12  mm.  in  length  by  5  to  6  mm.  in  breadth.  The  uterus  is 
composed  of  a  median  stem  with  7  to  10  lateral  branches  on  each 
side.  The  eggs  are  globular,  30  to  36  microns  in  diameter,  the 
shell  radially  striated,  and  the  oncosphere  contains  9  hooks. 

The  symptoms  of  infestation  with  the  pork  tapeworm  do  not 
differ  from  those  of  the  beef  tapeworm.  The  anatomic  differ- 
entiation has  been  made  under  Tcenia  saginata. 

The  length  of  life  of  the  pork  tapeworm  is  not  definitely  known, 
but  it  may  infest  man  for  fifteen  years  or  more. 

Multiple  infections  are  much  more  common  with  this  worm 
than  with  the  beef  variety.  Hosier  and  Pfiefer-'^  recount 
infections  with  18,  21,  21,  33,  and  41  parasites. 

The  prophylactic  measures  against  the  armed  tapeworm  are 
identical  with  those  against  Tmnia  saginata  excepting  that  in 
the  former  the  meat  concerned  is  pork. 

On  account  of  the  danger  of  somatic  teniasis  in  case  of  infec- 
tion with  the  pork  tapeworm,  treatment  should  be  instituted 
immediately.  It  is  possible  for  the  patient  to  infect  himself 
with  cysticercus  by  swallowing  the  eggs  of  his  own  parasite  or  by 
eggs  gaining  access  to  the  stomach  by  reverse  peristalsis.  This 
does  not  occur  in  the  case  of  the  beef  tapeworm. 

The  treatment  is  the  same  as  laid  down  for  Tcenia  saginata. 

HYMENOLEPIS  NANA 

The  Dwarf  Tapeworm,  Tasnia  murina,  Taenia  nana,  Taenia  agyptica, 
Diplacanthus  nanus,  Hymenolepis  murina 

The  dwarf  tapeworm  was  found  in  man  for  the  first  time  by 
Bilharz  in  Cairo,  Egypt,  in  1851.  He  recovered  a  "countless 
number"  of  them  at  a  post-mortem  on  a  boy  who  had  died  of 
meningitis.  Besides  in  Egypt,  this  parasite  has  been  found  in 
England,  Italy,  Servia,  Russia,  Germany,  Siam,  Japan,  North 
and  South  America. 

Until  1909  only  thirty-three  cases  had  been  reported  in  the 
United  States,  seven  of  these  having  been  reported  by  me. 
These  cases  may  be  tabulated  as  follows: 


504  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Philadelphia,  1872,  Spooner^" i 

Galveston,  Texas,  1902,  Moore^'* i 

Charleston,  S.  C,  1902,  Stiles^'" i 

Macon,  Ga.,  1902,  Stiles--" 3 

Washington,  D.  C.,  1903-04,  Hygienic  Laboratory-'* 12 

Amarillo,  Texas,  1903,  Magnenat--' 4 

Fort  Porter,  N.  Y.,  1904,  Hallock'^J 2 

Statesville,  N.  C,  1906,  Stiles  and  Garrison-''' i 

Marianna,  Ark.,  1906,  Deaderick--' 4 

Brooklyn,  N.  Y.,  1906,  Lambert^^'i i 

Marianna,  Ark.,  1907,  Deaderick^^^ i 

Marianna,  Ark.,  1909,  Deaderick"* 2 

Within  the  past  four  years  the  dwarf  tapeworm  has  been 
shown  to  be  the  commonest  cestode  in  the  South.  During  the 
three  years,  1911-1913  of  56,543  infections  found  by  the  Rocke- 
feller Sanitary  Commission  1,879,  '^^3-3  P^r  cent.,  were  Hymeno- 
lepis  nana.  It  has  been  found  in  all  Southern  States  surveyed 
by  this  Commission.  Schloss^^"  reports  twenty  cases  in  280  con- 
secutive examinations  in  New  York. 

Negroes  are  affected  as  well  as  whites.  Males  are  affected 
more  frequently  than  females. 

Children  from  live  to  ten  years  of  age  are  most  susceptible  to 
infestation,  but  no  age  seems  exempt,  cases  being  recorded  past 
fifty  years  of  age. 

The  only  intermediate  hosts  yet  determined  are  the  rat  and 
probably  man;  the  definitive  hosts  are  man  and  a  certain  species 
of  rats  and  mice. 

Direct  infection  from  man  to  man  seems  possible.  In  sup- 
port of  this  are  the  two  cases  of  Stiles--"  in  an  orphan  asylum, 
members  of  the  staff  of  the  Hygienic  Laboratory-"  finding  five 
cases  in  the  same  ward  of  an  insane  asylum/  Magnenat's--^  four 
cases  in  the  same  family,  and  my--®  two  cases  in  the  same  house- 
hold. In  all  of  Schloss'--''  cases,  with  one  exception,  more  than 
one  child  in  each  family  was  infected.  Venuti^'  found  twenty- 
three  cases  among  214  boys  examined  in  an  institution  in 
Catania,  while  no  cases  could  be  found  among  100  boys  of  the 
general  population. 

The  usual  mode  of  infection  seems  to  be  the  ingestion  of  food 
soiled  by  the  excrement  of  infested  rats  and  mice. 

The  length  of  my  specimens  of  Hymenolepis  nana  has  been 


OTHER  INTESTINAL  PARASITES  505 

from  8  to  18  mm. ;  the  breadth  of  mature  proglottides  from  0.33 
to  0.58  mm.;  and  the  number  of  segments  approximately 
from  100  to  200.  In  a  specimen  measuring  15  mm.  in  length 
there  were  185  segments.  The  head  is  subglobular,  elongated, 
possessed  of  a  retractile  rostellum  surrounded  by  a  single  row 
of  booklets,  numbering  from  twenty-two  to  thirty,  and  has  four 
suckers.  The  average  length  of  the  head  with  rostellum  pro- 
truded was  0.34  mm.,  with  rostellum  retracted  0.27  mm.,  and 
the  width  of  the  head  0.27  mm.  The  diameter  of  the  suckers 
averaged  86  microns.  The  booklets  averaged  14  microns  in 
length.  The  neck  is  slender  and  unsegmented.  In  a  specimen 
measuring  15  mm.  the  distance  from  the  tip  of  the  rostellum 
to  the  first  segment  was  1.18  mm.;  the  breadth  of  the  neck 
0.14  mm.  The  segments  of  the  strobila  gradually  increase  in 
breadth  toward  the  posterior  extremity,  the  last  fifteen  to 
forty  proglottides  being  usually  stuffed  with  ova.  Occa- 
sionally a  sterile  segment  is  seen  between  two  fertile  ones. 
The  genital  pores  are  single,  near  the  anterior  border  of  the 
segment,  and  usually  on  the  left  side.  Each  oviparous  seg- 
ment may  contain  from  80  to  180  ova.  The  mature  ova  are 
round  or  slightly  oval,  averaging  in  my  cases:  outer  mem- 
brane 50  by  42  microns,  inner  membrane  32  by  30  microns. 
Between  the  outer  membrane  and  the  inner  one  which  en- 
closes the  membrane  is  a  hyaline  substance  which  surrounds 
the  latter  like  a  wide  halo.  Within  the  embryo  can  be  dis- 
tinguished six  booklets  lying  parallel  or  radially.  A  few  very 
delicate  filaments  may  commonly  be  detected  arising  from 
opposite  poles  of  the  inner  membrane  and  permeating  the 
hyaline  substance. 

I  have  examined  the  ova  in  my  last  three  cases  with  reference 
to  Foster's-^^  interesting  observations  on  the  movements  of 
the  embryo  within  the  ovum,  but  have  not  been  able  to  verify 
them. 

The  symptoms  are  similar  to  those  of  infection  with  the  beef 
tapeworm,  strikingly  exaggerated  in  children.  In  one  of  my 
cases  abdominal  pain,  diarrhea  and  vomiting  were  prominent; 
in  another  nausea,  vomiting,  dizziness,  headache  and  dyspnea; 
in  a  third  vomiting,  abdominal  pains,  headache,  dyspnea,  dizzi- 


5o6  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


Fig.  I02. — Scolex  of  hymenolepsis  nana,  enlarged. 


Fig.  103. — Hooklets  from  hymenolepis  nana,  enlarged: 
a,  lateral  aspect;  b,  view  from  edge. 


Fig.   loi. — Hymenolepis  Fig.  104. — Proglottides  of  hymenolepis  nana, 

nana,  enlarged.  enlarged. 


OTHER  INTESTINAL  PARASITES 


507 


ness  and  diarrhea.  A  boy  aged  eleven  developed  edema  of  the 
hands,  feet  and  legs  up  to  the  knees,  of  the  eyelids  and  upper  lip. 
A  young  girl  had  convulsions  every  time  she  had  a  slight  fever; 
this  was  promptly  stopped  by  removal  of  a  large  number  of 
dwarf  tapeworms. 

Many  cases  are  symptomless. 

The  appetite  may  be  increased,  decreased  or  otherwise  per- 
verted.     Abdominal    pain    is    frequent,    so    are    nausea   and 


Fig.   105. — Hymenolepis  nana,  proglottides  containing  ova. 

vomiting.  Gnawing  and  crawUng  sensations  are  occasion- 
ally complained  of.  The  bowels  may  be  loose,  regular  or 
constipated. 

Nervousness  and  disturbed  sleep  are  not  infrequent  manifes- 
tations. In  children  choreic  movements  and  convulsions  have 
been  recorded. 

A  slight  degree  of  anemia  is  not  uncommon.  In  seven  of  my 
cases  the  eosinophiles  varied  between  7.8  and  26  per  cent.  Of 
fourteen  cases  of  Schloss'^-'  seven  showed  eosinophilia  ranging 
from  6.5  to  22  per  cent.,  while  in  the  remaining  seven  cases 
these  cells  were  normal. 

I  have  not  found  Charcot  crystals  in  the  feces  of  any  of  my 
cases,  but  in  mounted  specimens  of  the  parasite,  have  frequently 


5o8  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

noticed  the  formation  of  these  crystals  at  points  where  the  worm 
was  lacerated  or  contused. 

Multiple  infestation  is  the  rule,  as  many  as  several  thousand 
occasionally  being  present  in  the  same  individual. 

Mixed  infestations  are  common,  the  combination  with  hook- 
worm being  the  most  frequent.  One  of  my  cases  showed  in 
addition  to  Hymenolepis  nana,  Ascaris  lumbricoides  and  Tri- 
chomonas intestinalis. 

The  infection  may  persist  for  several  years  if  untreated. 

The  diagnosis  depends  solely  upon  the  detection  of  the  ova  or 
parasites  in  the  feces.  The  ova  are  likely  to  be  confounded  with 
no  others  excepting  the  rare  parasite  Hymenolepis  diminnta. 
The  latter  may  be  distinguished  by  the  somewhat  larger  size, 
the  presence  of  two  other  membranes  with  delicate  radial  stria- 
tions  between,  and  by  the  absence  of  filaments  in  the  hyaline 
substance. 

Preventive  measures  consist  of  treating  promptly  and  radi- 
cally infested  persons,  guarding  against  pollution  of  food  or 
hands  with  feces  of  infested  persons  and  the  protection  of  food 
stuffs  from  rats  and  mice. 

Treatment. — The  most  efficient  vermifuge  in  these  cases  is 
male-fern.  It  should  be  given  as  for  the  treatment  of  the  beef 
tapeworm.  While  the  worms  are  readily  expelled  by  this  agent, 
an  analysis  of  the  cases  in  which  the  results  of  treatment  by  male- 
fern  were  verified  by  subsequent  microscopic  examination  of 
the  feces  shows  that  more  than  one  treatment  is  usually  neces- 
sary. There  are  twenty-two  cases  in  which  the  results  were 
thus  followed  up.  Of  these  there  are  only  five  cases  in  which 
no  ova  were  found  after  one  treatment  with  male-fern;  in  six 
cases  two  treatments  were  necessary;  in  five  cases  three  doses 
were  needed;  in  one  case  four  or  five  treatments  were  adminis- 
tered; in  four  cases  after  one  dose  the  ova  were  still  present 
but  no  further  treatment  is  recorded;  in  one  case  after  several 
treatments  the  ova  persisted  in  the  feces;  and  in  two  of  the 
cases  in  which  three  doses  were  given  the  ova  were  yet  found 
after  the  last  dose.  The  drug  should,  of  course,  be  given  only 
after  thorough  purgation  with  salines. 


OTHER   INTESTINAL   PARASITES  509 

HYMENOLEPIS  DIMINUTA 

Taenia  diminuta,  Taenia  leptocephala,   Hymenolepis  flavopunctata,  Taenia 
flavopunctata,  Taenia  flavomaculata,  Taenia  minima,  Taenia  varesina 

In  1858  Weinland  first  described  a  case  of  Hymenolepis  dimi- 
nuta occurring  in  man.  The  parasites  were  recovered  in  1852 
from  a  healthy  infant  nineteen  months  old.  Two  fragments 
labelled  as  coming  from  man  were  found  in  the  museum  at 
Alfort,  France,  by  Raillet  before  1810,  and  were  identified  as 
Hymenolepis  diminuta  by  both  Raillet  and  Zschokke. 

The  following  is  a  synopsis  of  cases  which  have  thus  far  been 
reported  in  man:--^ 

Alfort,  France,  by  Raillet,  before  1810 i  case. 

Boston,  1842,  Weinland i  case. 

Philadelphia,  1884,  Leidy i  case. 

Varese,  Italy,  1884,  Parona i  case. 

Catania,  Sicily,  1887-8,  Grassi i  case. 

San  Paulo,  Brazil,  1893,  Lutz i  case. 

Pisa,  Italy,  1895,  Sonsino i  case. 

Rio  Janeiro,  Brazil,  i8g6,  Magalhaes i  case. 

Centuripe,  Sicily,  1900,  Previtera 2  cases. 

Philadelphia,  1900,  Packard i  case. 

Marianna,  Ark.,  1906,  Deaderick^^^ i  case. 

Hanley  Falls,  Minn.,  1906,  Nickerson^^' i  case. 

Of  the  above  thirteen  cases  four  were  in  males,  five  in  females, 
and  in  four  the  sex  is  not  recorded. 


Fig.  106. — Ovum  of  hymenolepis  diminuta,  enlarged. 

The  ages  were  16  months,  19  months,  20  months,  2,  2,  3,  8, 
11,12  and  40  years,  the  ages  of  four  patients  not  being  recorded. 

According  to  Ransom^-^  the  number  of  worms  present  in  each 
individual  varied  from  one  to  four.     In  my  case  there  were  three 


Sio 


ENDEMIC    DISEASES    OF   THE    SOUTHERN    STATES 


or  four  specimens,  while  in  Nickerson's^^^  there  were  about 
twenty-five. 

No  marked  symptoms  have  been  recorded  in  any  of  the  cases. 
Increased  appetite,  nausea,  and  pain  in  the  epigastrium  were 
the  complaints  in  my  case.  Slight  "peevishness"  was  noted  by 
the  mother  of  the  child  in  Nickerson's  case.  In  my  case  the 
eosinophiles  were  7  per  cent. 

This  parasite  in  the  adult  stage  inhabits  the  intestine  of 
certain  species  of  rats  and  mice.     It  is  probably  accidental  in 


Fig.  107. — Hymenolepis 
diminuta,  natural  size. 


Fig.  108. — Scolex  of  hymeno- 
lepis diminuta,  enlarged. 


man.  The  larva  occurs  in  the  meal  moth,  the  earwig  and  cer- 
tain species  of  beetles.  Recent  experiments  of  Nickerson-^' 
implicate  certain  myriapods,  Fontaria  and  Julus,  as  interme- 
diate hosts  in  America. 

Hymenolepis  diminuta  is  from  20  to  60  cm.  in  length  and  up  to 
3.5  to  4  mm.  broad.  The  segments  number  from  600  to  1300. 
The  head  is  club  shaped,  0.2  to  0.5  mm.  in  diameter,  and  has  a 
rudimentary  unarmed  rostellum.  There  are  four  suckers.  The 
ova  resemble  those  of  Hymenolepis  nana.  The  average  of  ten 
measurements  of  ova  in  my  case  gave:  outer  membrane  35  by 
40  microns.     Some  were  slightly  bile  stained,  others  perfectly 


OTHER    INTESTINAL    PARASITES  51I 

clear.  The  outer  membrane  appears  thickened  or  doubled  and 
may  be  radially  striated.  No  filaments  are  found  in  the  hyaline 
substance  as  in  the  ova  of  the  dwarf  tapeworm. 

The  diagnosis  is  made  by  the  discovery  of  segments  of  the 
worm  or  its  ova  in  the  feces. 

Prophylaxis  of  infection  with  this  parasite  consists  of  guard- 
ing against  contamination  of  food  by  the  meal  moth,  rats,  mice, 
and  other  hosts. 


Fig.  109. — Hymenolepis  diminuta,  proglottides  containing  ova,  enlarged. 

Treatment. — Any  anthelmintic  or  merely  a  cathartic  is 
usually  successful  in  expelling  the  parasite.  In  the  thirteen 
cases  santonin  was  used  twice,  male-fern  three  times,  calomel 
once,  the  worm  was  expelled  without  medicine  once,  and  the 
anthelmintic  used  is  not  recorded  in  six  cases. 

STRONGYLOIDES  rNTESTINALIS 

Anguillula  intestinalis,  Anguillula  stercoralis,  Rhabdonema  strongyloides, 
Rhabdonema  intestinalis,  Leptodera  stercoralis,  Leptodera  intestinalis 

In  1876  Normand  treated  a  number  of  French  soldiers  re- 
turned to  Toulon  from  Cochin  China  suffering  severely  from 
diarrhea.     A  large  number  of  small  nematodes  in  the  feces  were 


SI2 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


identified  as  strongyloides  intestinalis .  Both  Normand  and 
Bavay,  who  made  a  careful  study  of  these  parasites,  regarded 
them  as  the  causative  factors  of  Cochin  China  diarrhea. 

The  geographic  distribution  at  large  seems  strikingly  in  con- 
formity with  that  of  hook-worm.  The  reports 
of  the  Rockefeller  Sanitary  Commission  for  the 
years  1911-1913  record  cases  in  Mississippi, 
North  Carolina,  Tennessee,  Alabama  and 
Georgia.  Cases  were  observed  in  Baltimore 
by  Strong-^^  and  Thayer,^^*  and  in  Tennessee 
by  Brush.^^^  I  observed  a  case  in  eastern 
Arkansas,  and  the  State  Director  of  Sanitation 
in  this  state^'^  informs  me  that  his  field  men 
have  found  twenty-one  cases  in  this  state  to 
June  30, 1 9 14.  Simon^'^  records  it  in  Louisiana. 
Besides  man  the  only  other  host  for  this 
parasite  appears  to  be  the  monkey. 

The  modes  of  infection  by  Strongyloides  in- 
testinalis are  two:  by  the  mouth  with  infected 
food  or  water,  and  by  the  skin  after  the  manner 
of  hook-worm  infection.  It  is  maintained  by 
Fulleborn  and  Torgau-^^  that  even  those  larvae 
which  are  swallowed  must  pass  through  the 
stomach  wall  into  the  vessels  and  by  way  of  the 
right  heart,  lungs,  trachea  and  esophagus  back 
to  the  stomach  and  intestines. 

The  complicated  life  cycle  of  this  parasite 
is,  according  to  Stiles,-^®  as  follows: 

I.  (a)  The  parasitic  adults,  inhabiting  the 
intestine,  are  parthenogenetic  females  measur- 
ing 2.2  to  3  mm.  long  by  34  to  70  microns 
broad.  The  eggs  are  deposited  in  the  intestinal 
lumen  of  the  host  or  in  galleries  in  the  intestinal 
mucosa  made  by  the  females,  and  develop  into 

(b)  Rhabditiform  embryos  200  to  240  microns  long  by  12 
microns  broad  which  may  grow  to  450  to  600  microns  long  by  16 
to  20  microns  in  diameter  by  the  time  they  are  discharged  with 
the  feces.     These  embryos  develop  within  two  or  three  days  into 


Fig.  no.- — Larva 
of  strongyloides  in- 
testinalis, enlarged. 


OTHER  INTESTINAL  PARASITES  513 

II.  (c)  Free-living  dioecious  adults.  The  males  measure 
0.7  mm.  long;  the  tail  is  curved  ventrally  to  form  a  hook;  the 
spicules  are  curved  and  38  microns  long.  The  females  measure 
I  mm.  long;  thevulvais  situated  slightly  posterior  to  the  equator 
of  the  body.  Each  female  develops  thirty  to  forty  eggs  which 
may  or  may  not  segment  in  the  uterus;  these  eggs  develop 
forming  the 

(d)  Free-living  rhabditiform  embryos  which  measure  220 
microns  long;  when  they  attain  a  length  of  550  microns  they 
moult  and   become 

(e)  Filariform  embryos.  This  is  the  infecting  stage  which 
enters  man  by  the  mouth  or  through  the  skin,  reaches  the  duo- 
denum and  upper  part  of  the  jejunum  and  develops  directly 
into 

{a)  The  parthenogenetic  females. 

Instead  of  the  cycle  a-b-c-d-e-a  an  abridged  cycle  a-b-e-a 
may  occur. 

Strongyloides  intestinalis  may  be  cultivated  by  adding  sterile 
water  to  the  feces  and  placing  in  the  sunlight. 

The  parthenogenetic  females  are  found  only  in  the  upper  part 
of  the  small  intestine. 

The  pathogenic  equation  of  this  worm  has  long  been  debated 
and  is  still  unsolved.  Earlier  writers  on  the  subject  were  con- 
fident of  an  etiologic  association  with  diarrhea.  Of  recent 
years  the  tendency  is  increasingly  to  belittle  this  relation.  In 
many  cases  in  which  the  parasite  is  associated  with  diarrhea, 
enam^ebas  and  other  organisms  have  been  found.  It  is  not 
infrequently  associated  with  hook-worm.  It  is  probable  that 
its  pathologic  status  is  not  important,  though  in  some  cases  it 
appears  to  excite  a  catarrhal  enteritis. 

The  diagnosis  is  possible  only  through  the  discovery  of  the 
rhabditiform  embryo  in  the  feces.  Occasionally  after  free 
purgation  strings  of  eggs  may  be  found. 

Treatment. — No  known  anthelmintic  is  of  any  particular 
value  in  the  treatment  of  infection  with  this  parasite.  Thymol 
is  most  frequently  recommended,  but  the  results  are  far  from 
satisfactory. 


514  ENDEMIC   DISEASES    OF   THE    SOUTHERN    STATES 

ASCARIS  LUMBRICOIDES 
Round  Worm,  Eel  Worm,  Lumbricoid  Worm 

This  worm  is  practically  cosmopoKtan.  The  only  country 
on  the  globe  in  which  it  is  not  endemic  is  said  to  be  Iceland.  It 
is  second  only  in  frequency  to  the  hook-worm  in  the  South,  one- 
third  of  all  infection  found  by  the  Rockefeller  Sanitary  Com- 
mission for  the  years  1911-1913  being  the  round  worm. 

The  negro  race  is  more  often  infested  than  the  white.  In 
some  sections  of  the  South  it  is  a  common  custom  for  the  little 
negroes  to  be  "wormed"  (treated  for  round  worms)  regularly 
every  year. 

While  seasons  are  not  known  to  influence  the  frequency  of 
their  occurrence,  in  my  experience  they  are  more  evident  in 
the  summer  and  fall.  The  fact  that  this  is  the  malarial  season 
is  probably  responsible  for  this,  since  febrile  conditions  cause 
the  wandering  and  expulsion  of  the  parasites. 

Females  seem  more  prone  to  infestation  than  males.  Chil- 
dren are  more  frequently  the  hosts  of  these  worms  than  are 
adults.  Miller"^  reports  an  interesting  case  in  a  child  of  three 
weeks.  After  the  separation  of  the  cord  ulceration  of  the  um- 
bilicus occurred  leading  to  perforation  of  the  intestine,  and  from 
the  resulting  fistula  a  round  worm  18  cm.  long  was  discharged. 
Stiles  and  Garrison^"  report  a  case  in  a  patient  over  eighty 
years  old.  These  writers  have  collected  534  cases  in  which 
the  age  was  given  and  which  are  distributed  as  follows: 

0-15  years 444 

15-30  years 3° 

30-50  years 35 

More  than  50  years 5 

Ascaris  liimbricoides  is  known  to  occur  in  man  only. 

An  intermediate  host  is  not  concerned  in  the  dissemination 
of  the  infection.  After  passing  out  with  the  feces  the  ova  in 
the  course  of  a  month  or  more  develop  embryos  within.  When 
these  ova  are  swallowed  the  contained  embryo  develops 
directly  into  the  adult  stage.  Freezing,  if  not  too  prolonged, 
and  drying  of  the  ova  at  ordinary  temperatures  do  not  destroy 
the  embryo,  and  they  may  be  blown  about  as  dust.     Infection 


OTHER    INTESTINAL    PARASITES 


515 


Fig.  III. — Ovum  of  ascaris  lumbricoides, 
enlarged. 

through  water,  vegetables  or  soiled 
hands  are  the  usual  methods. 
Stiles^  beUeves  that  flies  may  carry 
the  ova  in  their  intestines  and 
thus  spread  the  infection. 

The  worms  are  reddish  or  gray- 
ish yellow  in  the  fresh  condition. 
The  oval  cavity  is  surrounded  by 
three  papillae,  one  dorsal  and  two 
ventral.  The  body  is  round  and 
tapers  toward  both  extremities. 
The  male  is  15  to  25  cm.  in  length 
and  about  3  mm.  in  diameter. 
The  posterior  end  is  flexed  ven- 
trally.  The  females  are  20  to  40 
cm.  long  and  about  0.5  cm.  in 
diameter.  The  posterior  extrem- 
ity is  straight.  The  vulva  is  an- 
terior to  the  middle  of  the  body. 

The  ova  are  elliptical,  50  to  70 
microns  in  length  by  40  to  50 
microns  broad.  The  external 
covering  is  thickly  set  with  proc- 
esses and  usually  bile  stained. 
The  ova  are  deposited  before 
segmentation. 


Fig.  112. — Ascaris  lumbricoides, 
female,  natural  size 


5l6  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

It  is  probable  that  the  pathogenic  power  of  ascaris  lumbri- 
coides  depends,  besides  mechanical  disturbances,  upon  a  toxin. 
Goldschmidt-^"  records  the  symptoms  experienced  by  himself 
and  others  while  dissecting  fresh  ascaris.  The  first  dissection 
often  caused  no  symptoms,  but  a  repetition  was  followed  by 
tenderness,  irritation  of  the  respiratory  tract,  sneezing,  coryza, 
conjunctivitis  and  typical  asthmatic  attacks  recurring  period- 
ically, strikingly  resembling  hay  fever.  These  suggest  ana- 
phylactic phenomena.  By  the  intraperitoneal  injection  of  an 
aqueous  extract  of  Ascaris  lumbricoides  Herrick-'*^  produced  a 
notable  eosinophilia  after  previous  sensitization,  and  shows  that 
the  substance  causing  such  an  eosinophile  increase  is  a  protein. 
Flury-^^  has  shown  that  the  tissues  and  excreta  of  these  worms 
contain  numerous  compounds  capable  of  inducing  local  hyper- 
emia, inflammation  and  necrosis. 

Multiple  infections  are  the  rule,  from  two  to  six  being  the 
usual  number.  However,  large  numbers  may  be  present.  I 
have  felt  masses  of  these  worms  through  the  abdominal  wall. 
Raines-"*-  describes  the  unique  case  of  a  child  of  twenty  months 
who  discharged  834  worms  in  one  day,  634  the  next,  and  within  a 
short  period  1,992  in  all.  Fauconneau-Dupresne-'^  observed 
the  case  of  a  twelve-year-old  boy  who  passed  5,126  of  these 
worms  in  less  than  three  months. 

Many  cases  present  no  symptoms.  On  the  other  hand,  the 
symptoms  may  be  alarming.  The  commonest  manifestations 
are  fretfulness,  restless  sleep,  dreams,  itching  of  the  nose  and 
anus,  gritting  the  teeth,  meteorism,  nausea  and  vomiting. 
There  may  be  perversion  of  hearing,  taste,  sight  and  smell, 
vertigo,  hysteria  and  convulsions.  Other  digestive  symptoms 
are  dyspepsia,  griping  pains  in  the  abdomen,  irregular  bowels, 
diarrhea,  constipation,  increased,  deficient  or  perverted  appetite, 
malnutrition  and  jaundice.  I  have  seen  severe  dysenteric 
symptoms  subside  after  riddance  of  round  worms.  Anemia  is 
present  in  some  cases,  and  if  symptoms  are  present  the  blood 
shows  eosinophilia. 

At  times  infestation  with  eel  worms  assumes  dangerous  sig- 
nificance. This  is  especially  true  when  the  parasites  are  in  such 
numbers  as  to  cause  intestinal  obstruction,  or  when  they  pene- 


OTHER    INTESTINAL    PARASTIES  51 7 

trate  communicating  passages  or  cause  perforation.  Febrile 
conditions  cause  the  parasites  to  become  active,  and  it  is  often 
under  such  circumstances  that  these  accidents  occur.  The 
worms  may  escape  spontaneously  from  the  anus,  mouth  or  nose, 
or  may  be  vomited.  Perforation  into  the  thoracic  or  abdominal 
cavity  may  result,  or  the  parasite  may  enter  the  Eustachian  tube 
or  cause  suffocation  by  entering  the  trachea.  '  It  is  stated  that 
there  are  recorded  about  ninety  cases  in  which  round  worms 
have  entered  the  bile  ducts,  nine  cases  into  the  pancreatic  duct, 
and  over  twenty  cases  into  the  urinary  passages."  Over  eighty 
cases  are  recorded  in  which  the  worms  have  escaped  through 
the  body  wall  at  various  points. 

The  following  unique  case  occurred  in  my  practice:  A  colored 
boy,  aged  nine  years,  shot  himself  while  playing  with  a  41-caliber 
Derringer.  I  saw  him  several  hours  after  the  accident  occurred. 
The  ball  entered  the  abdomen  in  the  median  Hne  immediately 
above  the  symphysis  and  could  be  felt  beneath  the  skin  a  little 
to  the  left  of  the  anus.  There  was  some  abdominal  rigidity; 
he  had  vomited  once  and  his  bowels  had  moved  twice  with  blood 
in  both  actions.  He  had  urinated  once  and  the  urine  contained 
one  or  two  small  clots  of  blood.  The  temperature  was  102, 
pulse  120,  otherwise  good.  The  insanitary  surroundings  and 
lack  of  facilities  and  the  belief  that  the  course  of  the  bullet 
was  extraperitoneal  led  me  to  treat  the  case  expectantly. 
His  condition  did  not  get  any  worse  nor  did  he  pass  more  blood 
from  the  bowel  or  bladder.  A  week  or  ten  days  after  the  ac- 
cident he  began  to  have  difficulty  in  starting  the  flow  of  urine, 
which  would  sometimes  be  interrupted  suddenly  after  having 
been  started — typical  "  stammering  urination."  This  difficulty 
continued  until  the  fifteenth  day  after  the  accident,  when  a 
large  living  lumbricoid  worm  made  its  exit  from  the  bladder 
through  the  urethra.     The  boy  made  an  uneventful  recovery. 

The  diagnosis  is  easily  made  by  the  detection  of  the  ova  in 
the  feces  or  the  expulsion  of  the  worms. 

The  longevity  of  Ascaris  lumbricoides  is  not  known.  Eggs 
may  be  found  in  the  feces  about  a  month  after  infection. 

Prophylaxis  consists  of  abstaining  from  contaminated  food 
and  water,  infection  by  soiled  hands,  and  exclusion  of  flies. 


5l8  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Treatment. — The  cure  of  this  infection  is  easy,  santonin  being 
practically  a  specific.  The  dose  for  a  child  under  one  year  is 
}i  to  H  grain;  for  a  child  one  to  five  years  of  age,  i  or  2  grains; 
for  older  children,  2  or  3  grains.  It  is  well  to  combine  calomel 
with  the  vermifuge,  and  preliminary  diet  and  purge  should  be 
prescribed  as  for  teniasis.  The  treatment  is  usually  repeated 
once  or  twice  at  forty-eight-hour  intervals.  The  feces  should 
be  examined  periodically  to  ascertain  whether  the  cure  has 
been  radical. 

OXYURIS  VERMICULARIS 

Ascaris  vermicularis,  Fusaria  vermicularis,  Pin  Worm,   Seat  Worm, 
Thread  Worm,  Maw   Worm 

These  worms  are  practically  cosmopolitan.  Even  in  Iceland, 
where  the  round  worm  is  not  endemic,  oxyuris  is  enormously 
frequent.  In  the  Southern  States  they  do  not  seem  to  be  as 
common  as  they  were  in  former  years.  The  Rockefeller  Sani- 
tary Commission  has  found  them  in  each  of  the  states  surveyed, 
and  it  is  probable  that  they  occur  with  greater  relative  frequency 
than  their  figures  indicate,  since  statistics  based  on  ova  findings 
under-estimate  pin  worms  as  their  ova  are  not  as  numerous  in 
cases  of  infection  as  is  the  case  with  many  other  parasites. 

More  cases  are  observed  in  spring  and  summer  than  in  other 
seasons. 

Males  are  less  frequently  infested  than  females. 

Infections  are  found  from  early  childhood  to  old  age. 
Heller-''^  observed  a  case  in  a  child  of  five  weeks.  A  number 
of  cases  compiled  by  Stiles  and  Garrison'^'*  may  be  arranged 
according  to  age  as  follows: 

0-15  years 305  cases. 

15-30  years 20  cases. 

30-50  years 16  cases. 

More  than  50  years 3  cases. 

Oxyuris  vermicularis  is  not  known  to  occur  in  any  other  animal. 

No  intermediate  host  is  concerned  in  the  transmission  of  this 
parasite  from  one  person  to  another.  The  ova  gain  access  to 
the  alimentary  canal  of  man  through  infected  hands,  food,  or 
drink.     Reinfection  of  an  infected  individual  is  common  after 


.  OTHEE  INTESTINAL  PARASITES 


519 


Fig  .113. — Ovum  of  oxyuris  vermicularis,  enlarged. 

scratching  the  anus  and  putting  the  hands  to  the 
mouth  or  nose.  It  is  possible  that  flies  may  carry 
the  ova. 

The  worm  is  white  in  color.  The  female  is 
about  I  cm.  in  length  and  0.6  mm.  in  diameter, 
and  has  a  long  sharp-pointed  tail.  The  vulva  is 
in  the  anterior  half  of  the  body,  the  anus  in  the 
posterior  half.  The  male  is  3  to  5  mm.  in  length, 
the  body  curved  ventrally.  The  males  die  early 
and  are  not  often  seen  in  the  feces.  For  a  long 
time  it  was  not  known.  The  eggs  are  oval, 
flattened  on  one  side,  and  average  50  by  20 
microns.  The  sexes  are  usually  present  in  equal 
numbers.  The  worms  may  be  from  a  very  few  to 
so  many  that  the  mucous  membrane  of  the  gut 
looks  like  fur. 

Symptoms  are  usually  due  to  the  nocturnal 
wanderings  of  the  worms. 

These  consist  chiefly  of  irritation  of  the  anus, 

disturbed  sleep,  gritting  the  teeth,  and  itching  of 

the  nose.     Pain  in  the  lower  part  of  the  abdomen 

is  common  and  there  may  be  meteorism,  nausea,    Fig-  114-— Ox- 
,.       ,  .        .  ,-^_  .  ,      yuris    vermicu- 

diarrhea  or  constipation,     ihe  appetite  may  be  laris,  adult  fe- 

deficient,  increased  or  irregular.     Genital  irrita-  °^^'^'  enlarged. 

tion  leading  to  masturbation  is  observed  in  some  cases,  and  the 

worms  may  enter  into  the  vagina.     Enuresis  is  occasionally 

caused   by  pin   worms.     Loss   of  weight,   headache,   anemia, 

convulsions  and  chorea  may  exist. 


52C  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

Eosinophilia  above  5  per  cent,  existed  in  seventeen  of 
Schloss'^^^  twenty-two  cases. 

Numerous  cases  are  recorded  in  which  the  appendix  has 
been  invaded  by  pin  worms  with  resulting  appendicitis;  indeed 
it  was  at  one  time  erroneously  supposed  that  the  appendix  was 
the  nornial  habitat  of  these  parasites. 

A  diagnosis  of  this  infection  cannot  be  made  on  symptoms 
alone  and  usually  rests  on  the  discovery  of  adult  females  dis- 
charged from  the  rectum.  The  ova  may  be  found  in  the  feces 
in  the  majority  of  cases,  but  a  negative  result  does  not  exclude 
infection. 

Since  reinfection  is  common  it  is  impossible  to  determine 
the  length  of  life  of  the  individual  worms.  Infection  may 
persist  for  a  number  of  years,  however.  The  males  are  short 
lived. 

Prophylaxis. — Since  infection  is  carried  from  the  anus  to 
the  mouth  by  the  fingers,  the  hands  should  be  washed  after 
defecation  and  the  nails  kept  trimmed  and  clean.  Food 
should  be  guarded  against  contamination  and  flies  should  be 
excluded. 

In  outhning  the  treatment  it  should  be  considered  that  the 
normal  habitat  of  oxyuris  is  the  cecum,  and  only  impregnated 
females  descend  to  the  rectum  to  ovulate;  hence  the  treatment 
should  be  continued  for  several  weeks.  Internal  treatment 
should  at  the  outset  be  combined  with  irrigations,  and  santonin, 
given  as  recommended  for  ascaris,  is  the  most  useful  drug. 
Quassia  is  an  effective  irrigation.  It  should  be  used  as  an 
infusion  using  two  tablespoonfuls  of  the  chips  to  a  pint  of  hot 
water.  No  more  should  be  injected  than  can  be  retained  and 
it  should  be  given  with  the  buttocks  elevated,  or  in  the  knee- 
chest  position.  In  the  cases  where  this  has  failed  me  I  have 
usually  had  success  on  obtaining  a  fresh  supply  of  quassia. 
Strong  salt  water  used  in  the  same  manner  is  often  effective. 
For  the  anal  pruritus  weak  mercurial  ointment  or  zinc  oxide 
ointment  should  be  applied  locally  at  night.  Reinfection  should 
be  guarded  against  and  the  treatment  persisted  in  until  the 
cure  is  radical. 


OTHER    INTESTINAL    PARASITES  52 1 

TRICHURIS  TRICHIURA. 

Trichocephalus    dispar,  Trichocephalus  trichuris,   Trichocephalus  hominis, 
Ascaris  trichiura,  Whip-worm 

The  whip-worm  is  said  to  be  cosmopolitan.  It  ranks  third 
in  frequency  among  the  infections  found  by  the  Rockefeller 
Sanitary  Commission.  I  failed  to  find  ova  of  this  parasite  in 
about  500  examinations  in  the  Mississippi  River  "bottom" 
in  eastern  Arkansas. 

Infections  are  commoner  among  negroes  than  among  whites. 

The  frequency  of  this  parasite  is  sometimes  regarded  as  an 
index  to  the  sanitary  condition  of  a  community. 

Females  are  more  frequently  infested  than  males. 


Fig.  115. — Ovum  of  trichuris  trichiura,  enlarged. 

Infections  have  been  found  from  the  age  of  less  than  three 
months  until  old  age.  Stiles  and  Garrison-'''  collected  from 
the  literature  a  number  of  cases,  which  fall  according  to  age  in 
the  following  limits: 

0-15  years 4°° 

iS-3°  years 41 

30-50  years 66 

More  than  50  years 16 

Besides  in  man  the  whip-worm  is  found  in  certain  monkeys 
and  lemurs. 

No  intermediate  host  is  necessary  in  the  propagation  of 
infection,  the  partially  developed  ova  being  swallowed  with 
contaminated  water  or  food. 

The  whip-worm  has  a  thick  club-shaped  body  which  tapers 
radially  into  the  long  thread-like  neck.     The  male  is  40—45 


52  2  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

mm.  in  length,  the  female  45-50  mm.,  about  three-fifths  being 
comprised  by  the  anterior  portion  of  the  body.  The  anus  is 
terminal  and  the  vulva  is  situated  near  the  commencement  of 
the  posterior  portion  of  the  body.  This  part  of  the  body  in 
the  male  is  spirally  rolled  up.     The  ova  are  very  characteristic. 


b 


Fig.  116. — Trichuris  trichiura.    a,  Male;  b,  female,  enlarged. 

They  are  barrel-shaped,  possessed  of  a  thick  brownish  shell 
and  perforated  at  the  poles.  They  measure  about  50  microns 
in  length  by  about  23  microns  in  breadth. 

There  are  usually  about  a  dozen  worms  present,  but  thousands 
have  been  found  at  autopsy.     The  cecum  is  the  normal  habitat. 

This  parasite  can  no  longer,  as  formerly,  be  regarded  as  a 
harmless  commensal  of  man.  Various  theories  have  been 
adduced  to  explain  its  pathogenicity,  such  as  that  the  worm  is 


OTHER    INTESTINAL    PARASITES  523 

a  blood  sucker,  that  it  produces  a  toxin  or  hemolysin,  or  that 
it  causes  mechanical  injury,  but  none  of  these  is  satisfactory. 
It  is  known  that  the  whip-worm  transfixes  the  mucous  mem- 
brane, embedding  beneath  it  the  anterior  portion  of  the  body 
and  producing  hyperemic  or  even  eroded  areas,  but  these  are 
not  sufficiently  extensive  to  be  pathogenic. 

This  worm  has  been  accused  of  a  part  in  the  infection  with 
typhoid  fever  but  the  evidence  is  not  convincing. 

While  many  cases  present  no  symptoms  there  may  be 
anemia,  severe  nervous  symptoms  and  gastro-intestinal  dis- 
turbances, shortness  of  breath  on  slight  exertion,  dyspeptic 
manifestations,  vomiting,  diarrhea,  nervousness,  insomnia, 
and  even  convulsions  and  coma  are  symptoms.  There  is 
rarely  any  eosinophilia  in  these  cases,  contrary  to  the  case  in 
most  helminthic  infections.  There  are  a  number  of  fatal 
cases  on  record.  Metchnikoff^*^  emphasized  the  importance 
of  these  parasites  in  the  production  of  appendicitis. 

Accurate  diagnosis  can  be  made  only  by  examination  of 
the  feces. 

It  is  not  known  how  long  infection  with  whip-worms  may 
persist. 

Prophylaxis. — The  prevention  of  soil  pollution  and  care 
against  contamination  of  food  are  the  requisite  prophylactic 
measures. 

Treatment. — It  is  proverbially  difficult  to  rid  the  bowel  of 
these  unwelcome  guests.  Many  anthelmintics  bring  away  part 
but  none  is  known  to  be  specific.  Thymol  perhaps  has  the 
best  reputation.  High  enemas  of  solutions  of  benzene  have 
recently  been  used  with  apparent  success  and  this  treatment 
deserves  further  trial. 

BALANTIDroM  COLI 
Paramoecium  coli,  Holophyra  coli 

Infections  with  Balantidium  coli  have  been  found  in  Russia, 
Sweeden,  Finland,  Germany,  Italy,  North  and  South  America, 
Cuba,  Africa,  Sunda  Isles,  Cochin  China  and  the  Philippines. 
In  the  United  States,  Bel  and  Couret-'*"  reported  a  case  in 
Louisiana,   Gray-^^  three  cases  in  Arkansas,   I  observed  one 


524 


ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 


case  in  eastern  Arkansas,  Sistrunk-""  one  in  Minnesota,  and 
the  Rockefeller  Sanitary  Commission-^^  two  cases  in  North 
Carolina  and  one  in  Mississippi.  Altogether  less  than  150  cases 
have  been  recorded  in  man. 

Males  are  twice  as  frequently  infested  as  females. 

Adults  are  far  more  frequently  subject  to  this  infestation, 
but  two  cases  having  occurred  in  children. 

Association  with  pigs  or  the  preparation  of  sausage  predispose 
to  infection. 


Fig.   117. — Balantidium  coli,  enlarged. 

Four  cases  have  been  reported  in  the  same  household. -^^ 

Besides  man,  the  domestic  pig  and  certain  species  of  monkeys 
serve  as  hosts  for  halantidiuni. 

It  is  possible  to  acquire  this  infection  through  food  or  water 
infected  with  the  feces  of  pigs  or  through  eating  infected  hog 
meat. 

The  body  of  this  infusorium  is  nearly  oval,  one  side  being 
usually  somewhat  longer  than  the  other.  The  length  is  from 
0.06  to  o.  I  mm.  and  the  breadth  from  0.05  to  0.07  mm.  The  an- 
terior end  shows  the  short,  broad,  funnel-shaped  peristome. 
The  anus  is  terminal  at  the  posterior  end.  There  is  a  distinct 
ectosarc  thickly  set  with  ciha.  The  endosarc  shows  ordinarily 
two  contractile  vacuoles  and  phagocyted  particles.  The 
nucleus  is  commonly  bean-shaped.  Reproduction  occurs 
through  binary  fission  and  budding  conjugation  is  known  in 


OTHER    INTESTINAL    PARASITES  525 

this  parasite,  and  encystation  is  known  to  occur.  The  organ- 
isms are  highly  motile.  Bel  and  Couret-^^  were  unable  to 
cultivate  them. 

The  habitat  of  this  parasite  in  man  is  the  large  intestine. 
The  organisms  invade  the  coats  and  vessels  of  the  gut,  produc- 
ing ulcers,  hyperemic  or  a  hemorrhagic  condition  of  the  in- 
tervening mucosa,  and  swelling  of  the  mesenteric  glands. 

Nearly  all  infested  patients  suffer  with  diarrhea  or  dysentery. 
The  feces  are  liquid  and  contain  undigested  food,  mucus  or 
blood.  Tormina  and  tenesmus  are  frequent  symptoms,  and 
in  persistent  cases  there  may  be  anemia,  loss  of  weight  and 
edema.     Eosinophilia  is  present  in  many  cases. 

The  diagnosis  is  impossible  without  the  detection  of  the 
characteristic  organisms  in  the  feces. 

The  duration  of  the  infection  may  be  as  long  as  fifteen 
years.  The  mortality  in  in  cases  collected  by  Strong^"*^  was 
30  per  cent. 

Prophylactic  efforts  should  be  directed  against  infected  pigs. 

Treatment. — The  list  of  drugs  recommended  for  the  treat- 
ment of  the  condition  indicates  that  there  is  no  specific.  Ene- 
mas of  quinine  solutions  are  perhaps  more  highly  recommended 
than  other  measures.  Enemas  of  tannic  acid,  silver  nitrate, 
iodine,  acetic  acid,  salicylic  acid,  and  boric  acid  have  been 
used.  Internal  treatment  has  so  far  been  unavailing.  Em- 
etine should  be  given  a  trial. 

MYIASIS  INTESTINALIS 

In  1902  Schlesinger-""  was  able  to  find  in  the  literature  some 
100  cases  of  intestinal  myiasis.  Since  then  a  number  of  such 
cases  have  been  recorded.  I  have  observed  two  cases  in 
Arakansas.-^^ 

Most  of  the  cases  are  reported  in  adults,  but  children  of  one 
year  or  under  may  be  affected. 

As  is  well  known,  the  larval  stage  of  some  diptera  is  neces- 
sarily passed  in  the  alimentary  canals  of  mammals  and  other 
animals,  for  instance,  the  bot-fly  of  cattle,  but  fly  larvae  must 
be  regarded  as  accidental  parasites  of  man. 


526  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

The  following  species  may  give  rise  to  intestinal  myiasis  in 
this  chmate: 

Musca  domestica,  the  common  house-fly,  deposits  its  eggs 
on  horse  manure,  occasionally  on  that  of  the  cow,  or  even  in 
human  feces,  rarely  on  decaying  animal  or  vegetable  matter. 

Musca  voniitoria,  the  blue  bottle  meat  fly,  deposits  its  ova 
by  preference  upon  decaying  animal  matter. 

Anthomyia  canicularis,  the  little  house-fly,  deposits  ova  upon 
decaying  vegetable  matter. 

Chrysomyia  macellaria,  the  screw-worm  fly,  deposits  ova  in 
wounds  or  on  decaying  flesh. 

Sarcophaga  carnaria,  the  green  flesh  fly,  larvs  placed  on  de- 
composing animal  matter,  possibly  also  on  human  feces. 

Piophila  casei,  the  cheese  fly,  deposits  its  ova  upon  human 
feces. 

Eristalis  tenax,  the  drone  fly,  the  larvas  are  found  on  decaying 
animal  and  vegetable  matter,  in  soft  mud  and  in  foul  water. 

These  creatures  may  gain  entrance  to  the  body  either  as 
ova  or  as  larvae.  Probably  the  most  common  mode  of  infec- 
tion is  through  eating  food  containing  ova  or  larvae,  though  the 
anus  may  be  the  port  of  entry.  Wirsing-"-  believes  that  in- 
fection occurred  through  the  anus  in  the  case  of  a  breast  nurs- 
ing infant  taking  an  air  bath  in  an  open  window.  In  the  case 
reported  by  Finlayson^^^  due  to  Anthomyia  canicularis,  it  ap- 
pears that  the  ova  were  not  swallowed  but  were  deposited  at 
the  anus  while  the  patient  was  defecating  and  were  taken  up 
within  the  bowel  after  defecation.  Nicholson^^''  reports  three 
cases  of  infection  with  larvae  of  Musca  domestica  in  which  it 
seems  probable  that  infection  was  by  way  of  the  anus.  Pro- 
lapse, hemorrhoids  and  external  lesions  predispose  to  such 
infections.  It  is  possible  that  infestation  may  occur  through 
the  swallowing  of  pregnant  viviparous  flies,  as  sarcophaga. 

Among  the  species  of  this  order  of  insects  whose  larvae  occur 
in  man  as  pseudoparasites  there  are  two  modes  of  reproduction, 
the  oviparous  and  the  viviparous.  The  former  is  the  more 
frequent  among  the  species  in  question,  but  the  latter  is  usual 
among  the  sarcopagids  especially  with  Musca  domestica;  each 
female  lays  about  120  eggs;  the  duration  of  the  egg  stage  is 


OTHER  INTESTINAL  PARASITES  527 

about  eight  hours,  of  the  larval  stage  about  five  days,  and  the 
pupa  stage  the  same.  These  figures  vary  with  the  cUmate 
and  season. 

The  symptoms  produced  by  these  loathsome  creatures  are 
abdominal  pains,  nausea,  diarrhea,  dysentery,  nervousness, 
abdominal  tenderness,  crawling  sensations  in  the  bowels,  mi- 
grain,  neuralgia  and  even  hysterical  symptoms  and  convulsive 
seizures. 

The  longevity  of  intestinal  maggots  is  not  known,  but  in- 
fection may  persist  for  years.  One  case  is  recorded  of  twelve 
years'  standing. ^°^ 

The  broad  diagnosis  of  intestinal  myiasis  is  easy  to  any  one 
familiar  with  the  ordinary  parasites,  but  a  specific  determina- 
tion should  not  be  attempted  by  any  one  but  an  expert.  In  all 
these  cases  it  is  well  to  breed  out  the  maggots  to  mature  insects 
as  determination  is  much  easier  in  the  adult  state.  A  little 
earth  in  a  pot  covered  by  gauze  is  all  that  is  necessary  for  this 
experiment. 

P*rophylaxis  consists  of  prevention  of  access  of  flies  to  food 
and  avoidance  of  defecation  in  the  open,  especially  by  those 
predisposed  by  anal  or  rectal  disease. 

The  treatment  which  is  usually  successful  is  castor  oil, 
alone,  or  given  with  santonin.  The  oil  should  be  given  on  an 
empty  stomach,  one  dose  for  three  successive  days.  In  one  of 
my  cases,  an  infestation  with  Chrysomyia  macellaria,  I  used  an 
enema  of  a  pint  of  cotton-seed  oil  with  a  satisfactory  result. 


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^1  Burot  and  Legrand,  Maladie  du  Soldat  aux  Pays  Chauds,  Paris,  1897. 
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34 


530  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

'2  Mowbray,  Lancet,  London,  Aug.  26,  1905. 
^3  Schlayer,  Deutsch.  med.  Wchnschr.,  July  10,  1902. 
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5'^  Koch,  Jour.  Trop.  Med.,  July  15,  1899. 

^^  Burot  and  Legrand,  Therapeutique  du  Paludisme,  Paris,  1897. 
5'  LeDantec,  Pathologic  Exotique,  Paris,  1905. 
8«  Kelsch  and  Kiener,  Maladies  des  Pays  Chauds,  Paris,  1889. 
'^  Dryepondt  and  Vancampenhout,  Jour,  de  med.  de  Bruxelles,  1899,  9. 
"» Bertrand,  Am.  Soc.  Med.-Chi.  d'Anvers,  Nov.-Dec,  1899. 
"1  Mould,  Brit.  Med.  Jour.,  Sept.  9,  1899. 
"2  Haig,  Lancet,  London,  Apr.  2,  i8g8. 
i"'  Deaderick,  Jour.  Am.  Med.  Assn.,  June  i,  1907. 
"*  Mense,  Arch.  f.  Sch.  u.  Trop.  Hyg.,  iii,  2. 
i»5  Plehn,  Ibid.,  iii,  4. 
"^  Cardamatis,  Grece  Med.,  Apr.,  1900. 
^■"  Crosse,  Lancet,  London,  Jan.  6,  1900. 
^"^  Krauss,  Memphis  Med.  Month.,  Apr.,  1902. 
i»9  Thin,  Brit.  Med.  Jour.,  Sept.  i,  1900. 
''"  Curry,  Jour.  Am.  Med.  Assn.,  xxxviii,  1130. 
m  Ketchen,  Brit.  Med.  Jour.,  Nov.  10,  1906. 
^'^  Ruge,  Deutsch.  med.  Wchnschr.,  July  10,  1902. 
11^  Hartsock,  New  York  Med.  Jour.,  Sept.  13,  1902. 
i^""  Broden,  Trav.  du  Lab.  Med.  de  Leopoldville,  Brussels,  1906. 
1'*  Cardamatis,  Progres.  Med.,  Nos.  37-40,  1902. 
11^  Virchow's  Jahresbericht,  i,  1907. 

1"  Grattan,  Jour.  Roy.  Army  Med.  Corps,  Lond.,  1907,  ix,  237. 
"*  Kiilz,  Arch.  f.  Sch.  u.  Trop.  Hyg.,  xii,  242. 
^''  Atti  deUa  Societa  Per  gli  Studi  della  Malaria,  Rome,  1907. 
^^°  Stephens  and  Christophers,  Practical  Study  of  Malaria,  London,  1904. 
121  Orme,  Jour.  Trop.  Med.,  Feb.  i,  igo8. 
1^'  Koch,  Deutsch.  med.  Wchnschr.,  Feb.  i,  1900. 
^'^  French,  New  York  Med.  Jour.,  May  23,  i8g6. 
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^^*  Hopkins,  Dublin  Jour.  Med.  Sc,  June,  1903. 
'''  Rankin,  Brit.  Med.  Jour.,  Sept.  i,  1900. 
*"  Moffatt,  Brit.  Med.  Jour.,  Jan.  25,  1902. 
135  McElroy,  Jour.  Am.  Med.  Assn.,  xli,  605. 
""  Dubose,  Ibid.,  Mar.  11,  1899. 
"'  Hearsey,  Brit.  Med.  Jour.,  Jan.  26,  1901. 
1"  Shropshire,  Jour.  Am.  Med.  Assn.,  xli,  600. 
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'1  Boxer,  Brit.  Med.  Jour.,  May  7,  1904. 
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Baker,  Ibid. 
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532  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

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2*''' Metchnikoff,  Bull,  de  I'Acad.  de  Med.,  Paris,  1901,  pp.  301-309. 

^*^  Bel  and  Couret,  Jour.  Infect.  Dis.,  Oct.,  igio. 

^-i^  Grey,  St.  Louis  Med.  Rev.,  Apr.  27,  1907. 

•"  Sistrunk,  Jour.  Am.  Med.  Assn.,  Ivii,  1507. 

'"^  Reports  of  the  Rockefeller  Sanitary  Commission,  1911,  1912  and  1913. 

-■"  Strong,  Bureau  of  Government  Laboratories,  Bull.  No.  26. 

25"  Schlesinger,  Wien.  klin.  Wchnschr.,  Jan.  2,  1902. 

2*1  Deaderick,  New  Orleans  Med.  and  Surg.  Jour.,  Oct.,  1908,  and  one  unpublished 

case. 
252  wirsung,  Ztschr.  f.  Klin.  Med.,  Ix,  1-2. 

263  Finlayson,  Glasgow  Med.  Jour.,  Mar.,  1889. 
2"  Nicholson,  Jour.  Am.  Med.  Assn.,  liv,  1687. 

^^'  McCampbell  and  Corper,  Jour.  Am.  Med.  Assn.,  liii,  1160. 

««  Stitt,  Am.  Jour.  Trop.  Dis.,  i,  169. 

2"  Kohlheim,  Jour.  Am.  Med.  Assn.,  Ivi,  1503. 

25S  Personal  communication,  Dr.  Ferrell. 

-*'  Personal  communication.  Dr.  Garrison. 

260  Hrdlicka,  Physiological  and  Medical  Observations  among  the  Indians  of  the 

S.  W.  United  States  and  Northern  Mexico,  Wash.,  1908. 
^''  Ashford  and  King,  Am.  jNIed.,  Sept.  5-12,  1903. 
2S2  Preti,  Munchen.  med.  Wchnschr.,  Iv,  436. 
*^'  Calmette  and  Breton,  L'Ankylostomiase,  Paris,  1905. 

264  Whipple,  Jour.  Exper.  Med.,  Mar.,  1909. 
"**  Castellani,  Jour.  Trop.  Med.,  Sept.  i,  1910. 
266  Yoshida,  Arch.  f.  Sch.  u.  Trop.  Hyg.,  xii,  696. 
^"  Stiles,  South.  Med.  Jour.,  Apr.,  1912. 

^^^  Greene,  South.  Med.  Jour.,  Apr.,  1911. 
^''  MacDonald,  Jour.  Trop.  Med.,  Jan.  15,  1908. 
^"'  Calhoun,  Jour.  Am.  Med.  Assn.,  lix,  1075. 
"' Jervey,  Jour.  Am.  Med.  Assn.,  Ixiii,  151. 

''^  Lumsden,  Roberts  and  Stiles,  Pub.  Health  Reports,  Nov.  11,  1910. 
"^  Ashford,  Trans.  XVth   International    Congress   on   Hygiene    and    Demog- 
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"■*  Manson,  Lectures  on  Tropical  Diseases,  Chicago,  1905. 
"' Bozzolo,  Gior.  Internaz.  del.  Sc.  Med.,  1879. 


534  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

-"  Stiles  and  Boatwright,  Public  Health  Reports,  July  i8,  1913. 

2"  Bozzolo,  Jour.  Am.  Med.  Assn.,  Iviii,  i74S- 

='3  Stiles  and  Leonard,  Public  Health  Reports,  Jan.  17,  1913. 

2"  Bentley,  Indian  Med.  Gaz.,  xxix.  No.  4. 

2™  Babcock,  Am.  Jour.  Insan.,  July,  191 2. 

2^1  Harris,  Am.  Med.,  July  19,  1902. 

^"'^  Searcy,  Jour.  Am.  Med.  Assn.,  xlix,  37. 

^8^  Merrill,  Jour.  Am.  Med.  Assn.,  xlix,  940. 

28«  Babcock,  Jour.  S.  C.  Med.  Assn.,  Feb.,  1908. 

285  Bellamy,  Jour.  Am.  Med.  Assn.,  li,  397. 

2'^  Trans.  Nat.  Conference  on  Pellagra,  r909. 

2"  Williamson,  Jour.  Am.  Med.  Assn.,  liii,  717. 

^'8  Hewitt,  Jour.  Am.  Med.  Assn.,  liii,  1085. 

'8'  Pollock,  Jour.  Am.  Med.  Assn.,  liii,  1087. 

2'"  Albright,  South.  Med.  Jour.,  Mar.,  r9i2. 

^'1  Trans.  Nat.  Conference  on  Pellagra,  191 2. 

292  Grimm,  Public  Health  Reports,  Mar.  7-14,  1913. 

293  Walker,  Jour.  Am.  Med.  Assn.,  July  3,  1909. 
2''!  Tucker,  Jour.  Am.  Med.  Assn.,  Jan.  28,  1911. 

295  First  Prog.  Kept.,  Thompson-McFadden  Pell.  Com.,  1913. 

295  Sambon,  Jour.  Trop.  Med.,  xiii,  271-319 

29'  Wood,  A  Treatise  on  Pellagra,  New  York,  191 2. 

298  Siler,  Garrison  and  MacNeal,  Jour.  Am.  Med.  Assn.,  Sept.  26,  1914. 

299  Albright,  South.  Med.  Jour.,  Mar.,  I9r2. 
'""'  Roberts,  Pellagra,  St.  Louis,  1912. 

201  Wolff,  South.  Med.  Jour.,  Mar.,  1912. 

""-  Clark,  Am.  Jour.  Trop.  Dis.,  Dec,  1914. 

'95  Beall,  Jour.  Am.  Med.  Assn.,  Nov.  18,  r9ii. 

""*  Lavinder,  Public  Health  Reports,  July  25,  1913- 

^°5  Niles,  Pellagra,  PhUa.,  191 2. 

'o^Lowery,  Med.  Rec,  New  York,  Aug.  29,  1914- 

=9'  Haase,  Jour.  Am.  Med.  Assn.,  July  6,  I9r2. 

'98  Marie,  Pellagra,  Columbia,  S.  C,  1910. 

='«9  De  Giaxa,  Annali  d'Igiene  Sper.,  Roma,  1892  and  1903. 

^■•9  Neusser,  Wien.  med.  Presse,  18S7. 

^1'  Public  Health  Reports,  Feb.  24,  1911. 

^12  Cini,  Rivista  Sper.  di  Freniat.,  etc.,  1902. 

"8  Tizzoni,  Estratto  del  Boletino  del  Minist.  di  Agricolt.,  Indust.  e.  Comm., 

Rome,  1909. 
'"  Mizell,  The  Journal  Record  of  Medicine  of  Atlanta,  1911. 
''5  Lavinder,  Pellagra,  A  Precis,  Public  Health  Bulletin,  48. 
315  Goldberger,  Public  Health  Reports,  Sept.  11,  1914. 
31'  Alessandrini  and  Scala,  Ed.  Jour.  Am.  Med.  Assn.,  Sept.  5,  1914- 

318  Sambon,  Cin.  Lancet-Clinic,  Oct.  25,  1913. 

319  Krause,  South.  Med.  Jour.,  March,  1912. 

320  Page,  Ibid.,  Feb.,  r9r5. 

3"  Sanders,  Ibid.,  March,  1915. 

322  Sambon,  Jour.  Trop.  Med.  and  Hygiene,  Oct.  15,  1910. 

328  Anderson  and  Goldberger,  Public  Health  Reports,  June  30,  191 1. 


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'"  Cranston,  Ibid.,  May  18,  191 2. 

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536  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

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^'^  Leroy,  South.  Med.  Jour.,  Mar.,  191 2. 

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"'  Grassi,  Gaz.  mad.  Ital.,  Lombardia,  1879,  P-  4451  Ibid.,  1882,  xxiv,  p.  135. 

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^'^  Gasser,  Arch,  de  med.  exper.  et  d'anat.  path.,  1895. 

^''  Quincke  and  Roos,  Berl.klin.  Wchnschr.,  1893. 

^'^  Kruse  and  Pasquale,  Ztschr.  f.  Hyg.,  1893. 

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^'^  Saundby  and  Miller,  Brit.  A'led.  Jour.,  1909. 

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408  whitmore,  Am.  Jour.  Trop^Dis.  and  Prev.  Med.,  Sept.,  1913. 

""  Craig,  Jour.  Med.  Research,  April,  191 2. 

"'"  Schaudinn,  Arb.  a.  d.  k.  Gsndhtsamte.,  1903. 

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451  Williamson,  Brit.  Med.  Jour.,  Sept.  14,  1901. 
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538  ENDEMIC    DISEASES    OF    THE    SOUTHERN    STATES 

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463  Report  to  the  Malaria  Committee,  6th  Series,  London,  1902. 

'"  Russell,  Malaria  and  Injuries  of  the  Spleen,  Calcutta,  1880. 

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*^*  Pezopoulos  and  Cardamatis,  Arch,  de  Med.  des  Enfants,  Jan.,  1907. 

469  VVinslow,  Boston  Med.  and  Surg.  Jour.,  May  27,  1897. 

470  Peters,  Bull.  Johns  Hopkins  Hosp.,  June,  1902. 
"'  Moffat,  Brit.  Med.  Jour.,  May  4,  1907. 

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"'  Hitte,  These  de  Montpelier,  1902. 

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"^  Bel,  Jour.  Am.  Med.  Assn.,  U,  1993. 

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"*  Daniels,  Brit.  Med.  Jour.,  Jan.  26,  1901. 

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^^'  Banks,  Philippine  Jour.  Sc,  Dec,  1907. 

482  Austin,  Practitioner,  London,  Mar.,  1901. 

^'^  Smith  and  KUbourne,  Texas  or  Southern  Cattle  Fever,  Washington,  1893. 

■**'  Giles,  The  Gnats  or  Mosquitoes,  London,  1902. 

***  Pressat,  Le  Paludisme  et  les  Moustiques,  Paris,  1905. 

«"  Eysell,  Arch.  f.  Sch.  u.  Trop.  Hyg.,  xi,  6. 

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488  Mitchel,  Mosquito  Life,  New  York,  1907. 

*8'  Stephens,  Ann.  Trop.  Med.  and  Parasit.,  i,  Apr.,  1914. 

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*"i  Ewing,  Am.  Jour.  Med.  Sc,  Oct.,  1901. 

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'"'  Boehm,  Malaria,  vol.  i,  p.  191. 

™*  Thayer,  Am.  Jour.  Med.  Sc,  Nov.,  Dec,  189S. 

'"^  Anders,  Jour.  Am.  Med.  Assn.,  June  15,  1895. 

^"^  Atkinson,  Am.  Jour.  Med.  Sc,  July,  1894. 

607  Wurtz  and  Thiroux,  Diag.  et  Sem.  des  Malad.  Trop.,  Paris,  1905. 

™'  Cohen,  Am.  Jour.  Med.  Sc,  cxxxvi,  344. 

*"'  Rist  and  Boudet,  Pres.  Med.,  Dec.  4,  1907. 

"°  Berl.  klin.  Wchnschr.,  Aug.  24,  1885. 


KEFERENCES  539 

"1  Goth,  Zeitschr.  f.  Geb.  U.  Gynak.,  vii,  i,  1881. 

SI-  Bonfils,  Paludisme  et  Puerperalite,  Paris,  1885. 

613  Williams,  A  Text-book  of  Obstetrics,  New  York,  1903. 

s'*  Winfield,  New  York  Med.  Jour.,  Aug.  2,  1902. 

^'■'  Anders,  Pliila.  Hosp.  Repts.,  iv,  1895. 

''*  Loeffler,  Deutsch.  med.  Wchnschr.,  1901,  No.  42. 

s^''  Henson,  Malaria,  St.  Louis,  1913. 

s'^  Fornario,  Deutsch.  med.  Wchnschr.,  Jan.  22,  1903.    • 

*!'  McElroy,  Memphis  Med.  Month.,  Nov.,  1902. 

s-°  Atti  della  Soc.  per  gli  Studi  deUa  Malaria,  Rome,  1902. 

s^'  Plehn,  Weiteres  iiber  Malaria,  etc.,  Jena,  1901. 

S22  Delaney,  Brit.  Med.  Jour.,  Mar.  28,  1903. 

s-^  Cardamatis,  Bull.  Soc.  Med.  de  Gand.,  Feb.,  1901. 

'''*  Ross,  Lancet,  London,  Nov.  17,  igo6. 

^-''  Ross,  Ibid.,  Sept.  28,  1907. 

526  Med.  and  Surg.  History  of  the  War  of  the  Rebellion,  iii,  Med.  Vol. 

s"  Hagen,  Arch.  f.  Sch.  u.  Trop.  Hyg.,  iv,  iii. 

s^'  Jour.  Trop.  Med.,  vol.  xi. 

'"  Haw,  Jour.  Trop.  Med.,  Oct.  16,  1899. 

^^Laveran,  Bull.  Acad.  Med.,  Ixix,  32. 

s'l  Erni,  Arch.  f.  Sch.  u.  Trop.  Hyg.,  June,  1899. 

s'2  Annual  Reports,  U.  S.  P.  H.  and  M.  H.  S.,  1905-07. 

^'^  Medizinal  Berichte  iiber  die  Deutsch.  Schutzgeb     1903-06. 

^'^  Wood,  Practical  Medicine,  Phila.,  1847. 

5^5  Atti  della  Soc.  per  gli  Studi  deUa  Malaria,  Rome,  1901. 

"*  Ibid.,  1904. 

5"  Cardamatis,  Bull.  Soc.  Med.  Gand.,  Nov.,  1900. 

"8  Billet,  Rev.  de  Med.,  Dec,  1902. 

52'  Maurel,  Maladies  Paludeennes  a  la  Guyana,  Paris,  1883. 

5*°  Charity  Hospital  Reports,  New  Orleans,  1906-07. 

5"  Neer,  Jour.  Am.  Med.  Assn.,  1,  1890. 

''2  Atti  della  Soc.  per  gli  Studi  della  Malaria,  Rome,  1908. 

5"  Ibid.,  1904. 

"'  Bacelli,  Gaz.  degli  Osp.,  Feb.,  1890. 

5*5  Guttmann  and  Ehrlich,  Berl.  klin.  Wchnschr.,  1891,  39. 

"*  Carpenter,  Med.  Rec,  New  York,  Ixx,  165. 

5"  Goldbetger,  Public  Health  Reports,  Nov.  12,  i9r5. 


INDEX 


Abdominai.  forms  of  malaria,  ii6 
Abortion  and  malaria,  131 
Abscess  of  liver,  424,  433,  443 

and  malaria,  161 
Acute  malaria,  97 
Age  and  amebic  dysentery,  402 
and  blackwater  fever,  230 
and  hookworm  disease,  452 
and  malaria,  36,  137 
and  pellagra,  291 
Algid  malaria,  116,  165 
Altitude  and  amebic  dysentery,  401 
and  blackwater  fever,  233 
and  malaria,  28 
and  pellagra,  288 
Ameba  in  pellagra,  308,  312 
Amebic  dysentery,   clinical  history, 
419 
diagnosis,  427 
etiology,  401 

geographic  distribution,  398 
history,  395 
pathology,  413 
prognosis,  434 
prophylaxis,  436 
treatment,  438 
Anaphylaxis  and  blackwater  fever, 

245 
Anemia  in  malaria,  85 
Ankylostomiasis.        See    Hookworm 

Disease. 
Anopheles  crucians,  61 

maculipennis,  60 

mosqiiitoes,  50 
Ardent  fever,  115 
Ascaris  lumbricoides,  514 
Autoserotherapy  in  pellagra,  392 

Bacteria  in  pellagra,  303 
Balantidium  coli,  523 
Banti's  disease  and  malaria,  164 
Bass'  method  in  hookworm  disease, 
475 


Beta-naphthol,  492 
Bilious  pernicious  malaria,  118 
Biology  oi  malaria  parasites,  66 
Blackwater    fever,     a     disease     sui 
generis,  243 
and  malaria,  235 
clinical  history,  250   ■ 
diagnosis,  262 
etiology,  229 

geographic  distribution,  226 
history,  219 
pathology,  247 
prognosis,  265 
prophylaxis,  270 
treatment,  272 
Blood  in  amebic  dysentery,  422 
in  blackwater  fever,  256 
in  hookworm  disease,  468 
in  malaria,  106,  125,  142,  157 
in  pellagra,  349 
Bone-marrow  in  malaria,  93,  96 
Bowels  in  amebic  dysentery,  423 
in  malaria,  92,  96,  109,  125 
in  pellagra,  372 
Brain  in  amebic  dysentery,  418 
in  blackwater  fever,  249 
in  malaria,  93 
Breeding  places  of  mosquitoes,  50 

Cachexia  in  pellagra,  349 
malarial,  126 

treatment  of  malarial,  211 
Cancer  and  malaria,  137 
Carriers  in  hookworm  disease,  472 

in  malaria,  189 
Cause  of  death  in  blackwater  fever, 

58 
Cerebellum  and  malaria,  1 14 
Cerebrospinal  malaria,  112 
Change  of  residence  and  blackwater 
fever,  233 
and  malaria,  39 
Children  and  malaria,  137 


542 


Choleraic  pernicious  malaria,  117 
Chronic  malaria,  119 

treatment,  211 
Circulatory  system  and  malaria,  123 
Civil  condition  and  pellagra,  292 
Civilization  and  malaria,  40 
Climate  and  hookworm  disease,  451 
Clinical  history  of  amebic  dysentery, 
419 
of  black  water  fever,  250 
of  hookworm  disease,  462 
of  malaria,  97 
of  pellagra,  324 
Comatose  malaria,  112,  164 
Complications  of  amebic  dysentery, 
424 
of  black  water  tever,  259 
of  hookworm  disease,  472 
of  malaria,  123 
of  pellagra,  362 
Congenital  malaria,  42 
Contagion  of  pellagra,  302 
Convulsions  and  malaria,  115 
Corn  in  pellagra,  295 
Cultivation  of  amebae,  408 
of  malaria  parasites,  80 

Diabetes  and  malaria,  136 
Diagnosis  of  amebic  dysentery,  427 

of  blackwater  fever,  262 

of  hookworm  disease,  473 

of  malaria,  140 

of  pellagra,  369 

of  pernicious  malaria,  164 
Diaphoretic  pernicious  malaria,  117 
Diarrhea  in  pellagra,  341 
Diet  in  pellagra,  295,  386 
Differential  diagnosis  of 'malaria,  161 
Digestive  system  in  hookworm  dis- 
ease, 466 
Dirt  eating  in  hookworm  disease,  466 
Duration  of  hookworm  disease,  465 

of  pellagra,  361 
Dwarf  tapeworm,  503 
Dysenteric  malaria,  118 
Dysentery  and  malaria,  125 

Ear  in  malaria,  134 
Emetine  in  dysentery,  441 


Endamceba  coli,  406,  431 

hystolytica,  403,  427,  431 
Endemic  index  and  malaria,  37 
Endocarditis  and  malaria,  162 
Epidemics  of  amebic  dysentery,  403 

of  malaria,  41 
Estivo-autumnal  fever,  102 

parasites,  72 
Etiology  of  amebic  dysentery,  401 

of  blackwater  fever,  229 

of  hookworm  disease,  451 

of  malaria,  25 

of  pellagra,  287,  295 

of  pernicious  malaria,  85 
Experimental  blackwater  fever,  241 
Exposure  and  malaria,  40 
Eye  in  hookworm  disease,  471 

in  malaria,  133 

in  pellagra,  348 

Family  predisposition  to  blackwater 
fever,  231 

tendency  to  pellagra,  302 
Feces  in  amebic  dysentery,  423 

in  hookworm  disease,  467,  473 

in  pellagra,  358 
Flagella  of  malaria  parasites,  70 

Gametes,  70,  73 
Gangrene  and  malaria,  135 
Gastro-intestinal  tract,  313 
Generative  system  in  hookworm  dis- 
ease, 470 
Genito-urinary  organs  and  malaria, 

130 
Geographic    distribution    of    amebic 
dysentery,  398 
of  blackwater  fever,  226 
of  hookworm  disease,  448,  466 
of  malaria,  21 
of  pellagra,  285 
Goldberger's  theory,  299 
Ground  itch  in  hookworm  disease, 
465 

Heart  in  blackwater  fever,  249 
in  hookworm  disease,  467 
in  malaria,  93,  96,  123 
in  pellagra,  323 


543 


Hemoglobinuria,  253 

Hepatic  abscess  in  amebic  dysentery, 

424 
Heredity  and  pellagra,  292 
Hibernation  of  mosquitoes,  64 
History  of  amebic  dysentery,  395 
of  blackwater  fever,  219 
of  hookworm  disease,  445 
of  malaria,  17 
of  pellagra,  281 
Hookworm  disease,  clinical  history, 
462 
diagnosis,  473 
etiology,  451 

geographic  distribution,  448 
history,  445 
pathology,  460 
prognosis,  478 
prophylaxis,  480 
treatment,  487 
Hymenolepis  diminuta,  509 

nana,  503 
Hygiene  and  pellagra,  293 
Hygienic  treatment  of  malaria,  210 

Idiosyncrasy  and  blackwater  fever, 

231 

Immunity    and    amebic    dysentery, 

402 

and  malaria,  32 

and  pellagra,  303 

Incubation  in  malaria,  97 

in  pellagra,  326 
Individual  predisposition  in  malaria, 

88 
Infectivity  in  pellagra,  301 
Influenza  and  malaria,  136,  163 
Inoculation   experiments  in   amebic 
dysentery,  408 
of  malaria,  45 
of  pellagra,  308 
Insanity  in  pellagra,  343 
Intermediate  host  in  pellagra,  305 
Intestinal  parasites,  495 
and  malaria,  125 
and  pellagra,  362 
Intestine  in  amebic  dysentery,  413 
in  blackwater  fever,  249 
in  hookworm  disease,  460 


Intestine  in  pellagra,  315 
Inundations  and  amebic  dysentery, 
401 
and  malaria,  30 
Ipecac  in  dysentery,  440 

Jaundice  in  blackwater  fever,  254 

Kidneys  in  blackwater  fever,  248, 
259 
in  malaria,  92,  95,  130 
in  pellagra,  323 

Larva,  anopheles,  54 
Latent  malaria,  84,  119 
Length  of  residence  and  blackwater 
fever,  232 
and  malaria,  39 
Leucocytes  in  malaria,  108 
Leukemia  and  malaria,  164 
Liver  abscess  in  amebic  dysentery, 
424 
in  blackwater  fever,  248 
in  malaria,  91,  94 
in  pellagra,  323 
Lumbricoid  worm,  514 
Lungs  in  blackwater  fever,  249 
in  malaria,  92,  96 
in  pellagra,  322 
Localizations  of  parasites  in  malaria, 
87 

Macrogametes,  71,  75 

Maggots,  525 

Malaria,  cachexia  in,  126 

clinical  history,  97 

chronic,  119 

diagnosis,  140 

etiology,  25 

geographic  distribution,  21 

history,  17 

pathologic  anatomy,  90 

pernicious,  1 11 

prognosis,  166 

prophylaxis,  172 

treatment,  197 
Malarial  mosquitoes,  46,  50,  59 

paroxysms,  97 
Malignant  tertian  fever,  103 


544 


Masked  malaria,  123 

Mental  symptoms  in  pellagra,  343, 

373 
Methylene  blue  in  malaria,  214 
Microgametocytes,  71,  75 
Mode  of  infection  in  amebic  dysen- 
tery, 410 
in  hookworm  disease,  453 
in  malaria,  42 
Moisture  and  hookworm  disease,  451 
Mortality  of  amebic  dysentery,  434 
of  blackwater  fever,  266 
of  hookworm  disease,  474 
of  malaria,  168 
of  pellagra,  378 
Mosquitoes  and  malaria,  46 

destruction  of,  177 
Muscular  system  in  hookworm  dis- 
ease, 470 
Myiasis  intestinalis,  525 

Negator  americanus,  454 
Negro  and  malaria,  138 
Nephritis  in  blackwater  fever,  259 

in  malaria,  130 
Nervous  system  in  hookworm  dis- 
ease, 470 
in  malaria,  iii,  112,  132 
in  pellagra,  342,  373 
Number  of  parasites  in  malaria,  86 

Occupation  and  amebic  dysentery, 
402 

and  blackwater  fever,  334 

and  hookworm  disease,  452 

and  malaria,  39,  375 

and  pellagra,  292 
Ova  of  hookworm,  457 

of  mosquitoes,  51 
Oxyuris  vermicularis,  518 

Parasites,    frequency,    in    malaria, 
151 

of  amebic  dysentery,  403 

of  blackwater  fever,  236 

of  hookworm  disease,  450 

of  malaria,  64,  74 

of  pellagra,  298,  303 
Paralysis  in  malaria,  114,  132 


Paroxysms  in  malaria,  97 
Parthenogenesis,  77 
Pathogenesis   of  amebic   dysentery, 
411 

of  blackwater  fever,  235 

of  hookworm  disease,  458 

of  malaria,  82 

of  pellagra,  311 
Pathology  of  amebic  dysentery,  413 

of  blackwater  fever,  247 

of  hookworm  disease,  460 

of  malaria,  90 

of  pellagra,  313 
Pellagra,  clinical  history,  324 

diagnosis,  369 

etiology,  287 

geographic  distribution,  285 

history,  281 

pathology,  313 

prognosis,  374 

prophylaxis,  380 

sine  pellagra,  361 

treatment,  385 
Periodicity  in  malaria,  140 
Pernicious  malaria,  xi i 
diagnosis,  164  ■ 
etiology,  85 
prognosis,  169 
treatment,  216 
Pin  worm,  518 
Plasmodium  tenue,  65 
Pneumonia  and  malaria,  116,  125 
Pork  tapeworm,  501 
Prevention  of  blackwater  fever,  270 

of  hookworm  disease,  480 

of  malaria,  172 
Pregnancy  and  pellagra,  364 
Previous     attacks     of     blackwater 
fever,  231 

malaria  and  blackwater  fever,  235 
Prognosis  of  amebic  dysentery,  434 

of  blackwater  fever,  265 

of  hookworm  disease,  478 

of  malaria,  166 

of  pellagra,  374 
Prophylaxis    of    amebic    dysentery, 
436 
of  blackwater  fever,  270 
of  hookworm  disease,  480 


545 


Prophylaxis  of  malaria,  172 

of  pellagra,  380 
Pseudopellagra,  364 
Puerperal   septicemia   and   malaria, 

162 
Pupa  of  anopheles,  58 

Quartan  fever,  loi 

parasites,  71 
Quinine,  absorption  and  elimination, 
197 

action  on  parasites,  200 

and  blackwater  fever,  224,  239 

choice  of  preparation,  202 

contra-indications,  201 

dose,  208 

in  blackwater  fever,  272 

in  malaria,  197 

methods  of  administration,  203 

prevention  of  malaria,  190 

substitutes,  214 
Quotidian  estivo-autumnal,  105 

Race  and  amebic  dysentery,  401 
and  blackwater  fever,  229 
and  hookworm  disease,  452 
and  malaria,  32,  138 
and  pellagra,  289 
Rainfall  and  malaria,  26 

and  pellagra,  288 
Recurrences  in  pellagra,  364 
Relapse  in  malaria,  84,  1 19 
Relative  frequency  of  malaria,  24 
Respiratory    organs    in    hookworm 
disease,  469 
in  malaria,  109,  124 
Round  worms,  514 

Salvaesan  in  malaria,  216 

Schizogonic  cycle,  67 

Season  and  amebic  dysentery,  401 

and  blackwater  fever,  231 

and  hookworm  disease,  451 

and  malaria,  26 

and  pellagra,  287 
Sepsis  and  malaria,  162 
Sequels  of  blackwater  fever,  259 

of  hookworm  disease,  472 

of  malaria,  123 


Sex  and  amebic  dysentery,  402 

and  blackwater  fever,  230 

and  hookworm  disease,  452 

and  malaria,  36 

and  pellagra,  290 
Skin  and  malaria,  in,  134 

and  pellagra,  313,  327,  369 
Smallpox  and  malaria,  137 
Social  condition  and  hookworm  dis- 
ease, 453 
and  malaria,  40 
and  pellagra,  293 
Soil  and  hookworm  disease,  451 

and  malaria,  27 
Sources  of  error  in  malaria,  149 
Spinal  fluid  in  pellagra,  359 
Spleen  in  blackwater  fever,  247 

in  malaria,  91,  94,  125 

in  pellagra,  323 

rupture,  129 
Spontaneous    recovery    in    malaria, 
166 
in  pellagra,  374 
Sporogonic  cycle,  76 
Staining  ameba,  428 
Stains  for  malaria,  147 
Stomach  in  blackwater  fever,  249 

in  malaria,  92,  96,  109,  125 

in  pellagra,  315,  340,  356,  371 
Stomatitis  in  pellagra,  339 
Strongyloides  intestinalis,  511 
Surgery  and  blackwater  fever,  278 

and  malaria,  139 
Symptomatic  t'eatment  of  malaria, 

210 
Symptoms  of  amebic  dysentery,  419 

of  blackwater  fever,  250 

of  hookworm  disease,  462 

of  malaria,  97,  105 

of  pellagra,  324 
Syphilis  and  malaria,  137,  163 

T/Enia  saginata,  497 

solium,  501 
Tapeworm,  497,  501,  503,  509 
Technic  of  blood  examinations,  142 
Temperature  in  amebic   dysentery, 
421 

in  malaria,  105 


546 


Tertian  fever,  99 
parasites,  69 
Therapeutic  test  in  hookworm  dis- 
ease, 476 
in  malaria,  159 
Thoracic  forms  of  malaria,  116 
Thymol,  487 
Topography  and  malaria,  28 

and  pellagra,  288 
Toxin  in  malaria,  82 
Transfusion  and  pellagra,  391 
Trauma  and  malaria,  139 
Treatment  of  amebic  dysentery,  438 

of  blackwater  fever,  272 

of  hookworm  disease,  487 

of  malaria,  197 

of  pellagra,  385 
Trees  and  malaria,  30 
Trichocephalus  dispar,  521 
Trichuris  trichura,  521 
Typhoid  fever  and  malaria,  135,  163 
Typhoid  pellagra,  360 

pernicious  malaria,  115 


Typhomalarial  fever,  135 
Tuberculosis  and  malaria,  136,  163 

Uncinaria  americana,  454 
Uncinariasis.     See    Hookworm     dis- 
ease. 
Urine  in  blackwater  fever,  252 

in  hookworm  disease,  470 

in  malaria,  109 

in  pellagra,  355 

Vegetation  and  malaria,  30 

Wassermann   reaction   in    malariai 
108 
in  pellagra,  354 
Whipworm,  521 
Wind  and  malaria,  31      , 

Yellow  fever  and  blackwater  fever, 
262 
and  malaria,  163 


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The  illustrations  are  most  beautiful. 

Dr.  W.  G.   MacCallum,   Columbia  University 

"  I  have  looked  over  the  book  and  think  the  plan  is  admirably  carried  out  and  that  the 
book  supplies  a  need  we  have  felt  very  much.     I  shall  be  very  glad  to  recommend  it." 


Howell's  Physiology 


A  Text=Book  of  Physiology.  By  William  H.  Howell,  Ph.D., 
M.  D.,  Professor  of  Physiology  in  the  Johns  Hopkins  University,  Balti- 
more, Md.     Octavo  of  1020  pages,  306  illustrations.     Cloth,  I4.00  net. 

THE  NEW  (5th)  EDITION 

Dr.  Howell  has  had  many  years  of  experience  as  a  teacher  of  physiology  in 
several  of  the  leading  medical  schools,  and  is  therefore  exceedingly  well  fitted  to 
write  a  text-book  on  this  subject.  Main  emphasis  has  been  laid  upon  those  facts 
and  views  which  will  be  directly  helpful  in  the  practical  branches  of  medicine.  At 
the  same  time,  however,  sufficient  consideration  has  been  given  to  the  experimen- 
tal side  of  the  science.  The  entire  literature  of  physiology  has  been  thoroughly 
digested  by  Dr.  Howell,  and  the  important  views  and  conclusions  introduced  into 
his  work.  Illustrations  have  been  most  freely  used. 
The  Lancet,  London 

"  This  is  one  of  the  best  recent  text-books  on  physiology,  and  we  warmly  commend  it  to  the 
attention  of  students  who  desire  to  obtain  by  reading  a  general,  all-round,  yet  concise  survey  of 
the  scope,  facts,  theories,  and  speculations  that  make  up  its  subject  matter." 


PATHOLOGY 


Mallory  and  Wright's 
Pathologic  Technique 

Just  Issued — New  (6th)  Edition 

Pathologic  Technique.  A  Practical  Manual  for  Workers  in  Patho- 
logic Histology,  including  Directions  for  the  Performance  of  Autopsies 
and  for  Clinical  Diagnosis  by  Laboratory  Methods.  By  Frank  B. 
Mallory,  M.  D.,  Associate  Professor  of  Pathology,  Harvard  Univer- 
sity; and  James  H.  Wright,  M.  D.,  Pathologist  to  the  Massachusetts 
General  Hospital.  Octavo  of  538  pages,  with  160  illustrations.  Cloth, 
;g300  net. 

In  revising  the  book  for  the  new  edition  the  authors  have  kept  in  view  the 
needs  of  the  laboratory  worker,  whether  student,  practitioner,  or  pathologist,  for 
a  practical  manual  of  histologic  and  bacteriologic  methods  in  the  study  of  patho- 
logic material.  Many  parts  have  been  rewritten,  many  new  methods  have  been 
added,  and  the  number  of  illustrations  has  been  considerably  increased. 

Boston  Mediced  and  Surgical  Journal 

"  This  manual,  since  its  first  appearance,  has  been  recognized  as  the  standard  guid°  in  patho- 
logical technique,  and  has  become  well-nigh  indispensable  to  the  laboratory  worker." 


Eyre's   B&.cteriolog'ic   Technic 

Bacteriologic  Technic.  A  Laboratory  Guide  for  the  Medical, 
Dental,  and  Technical  Student.  By  J.  W.  H.  Eyre,  M.  D.,  F.  R.  S. 
Edin.,  Director  of  the  Bacteriologic  Department  of  Guy's  Hospital, 
London.     Octavo  of  520  pages,  2ig  illustrations.  Cloth,  ^3.00  net.  ■ 

NEW  (2d)   EDITION.  REWRITTEN 

Dr.  Eyre  has  subjected  his  work  to  a  most  searching  revision.  Indeed,  so 
thorough  was  his  revision  that  the  entire  book,  enlarged  by  some  150  pages  and 
50  illustrations,  had  to  be  reset  from  cover  to  cover.  He  has  included  all  the 
latest  technic  in  every  division  of  the  subject.  His  thoroughness,  his  accuracy,  his 
attention  to  detail  make  his  work  an  important  one.  He  gives  clearly  the  technic 
for  the  bacteriologic  examination  of  water,  sewage,  air,  soil,  milk  and  its  products, 
meats,  etc.  And  he  gives  you  good  technic — methods  attested  by  his  own  large 
experience.  To  any  one  interested  in  this  line  of  endeavor  the  new  edition  of 
Dr.  Eyre's  work  is  indispensable.      The  illustrations  are  as  practical  as  the  text. 


SAUNDERS'   BOOKS  ON 


McFarland's   Pathology 


A  Text=Book  of  Pathology.    By  Joseph  McFarland,   M.  D.,  Pro- 
fessor of  Pathology  and  Bacteriology  in  the  Medico-Chirurgical  College 
of  Philadelphia.     Octavo  of  856  pages,  with  437  illustrations,  many  in 
colors.     Cloth,  ^5.00  net;   Half  Morocco,  ^6.50  net. 
THE   NEW    (2d)    EDITION 

You  cannot  successfully  treat  disease  unless  you  have  a  practical,  clinical 
knowledge  of  the  pathologic  changes  produced  by  disease.  For  this  purpose  Dr. 
McFarland's  work  is  well  fitted.  It  was  written  with  just  such  an  end  in  view — to 
furnish  a  ready  means  of  acquiring  a  thorough  training  in  the  subject,  a  training 
such  as  would  be  of  daily  help  in  your  practice.  For  this  edition  every  page  has 
been  gone  over  most  carefully,  correcting,  omitting  the  obsolete,  and  adding  the 
new.  Some  sections  have  been  entirely  rewritten.  You  will  find  it  a  book  weU 
worth  consulting,  for  it  is  the  work  of  an  authority. 

St.  Paul  Medical  Journal 

"  It  is  safe  to  say  that  there  are  few  who  are  better  qualified  to  give  a  resume  of  the  modem 
views  on  this  subject  than  IVIcFarland.     The  subject-matter  is  thoroughly  up  to  date." 

Boston  Medical  and  Surgical  Journal 

"  It  contains  a  great  mass  of  well-classified  facts.  One  of  the  best  sections  is  that  on  the 
special  pathology  of  the  blood." 


McFarland's 

Biolog'y:  Medical  and  General 

Biology:   Medical  and  General By  Joseph  McFarland,  M.  D., 

Professor  of  Pathology  and  Bacteriology  in  the  Medico-Chirurgical  Col- 
lege of  Phila.      i2mo,  457  pages,  160  illustrations.     Cloth,  ^1.75  net. 

NEW  (2d)   EDITION 

This  work  is  both  a  gcjieral  and  7nedical  biology.  The  former  because  it  dis- 
cusses the  peculiar  nature  and  reactions  of  living  substance  generally;  the  latter 
because  particular  emphasis  is  laid  on  those  subjects  of  special  interest  and  value 
in  the  study  and  practice  of  medicine.  The  illustrations  will  be  found  of  great 
assistance. 

Frederic  P.  Gorham,  A.  M.,  Brown  University. 

"  I  am  greatly  pleased  with  it.  Perhaps  the  highest  praise  which  [  can  give  the  book  is  to 
say  that  it  more  nearly  approaches  the  course  I  am  now  giving  in  general  biology  than  any 
other  work." 


BA CTERIOL OG Y  AND   HISTOLOG Y. 


McFarland's  Pathogenic 
Bacteria    and    Protozoa 

Pathogenic  tJacteria  and  Protozoa.  By  Joseph  McFarland,  M.D., 
Professor  of  Pathology  and  Bacteriology  in  the  Medico-Chirurgical 
College  of  Philadelphia.  Octavo  of  878  pages,  finely  illustrated. 
Cloth,  ;^3.50  net. 

NEW  (7th)  EDITION,  ENLARGED 

Dr.  McFarland  has  subjected  his  book  to  a  most  vigorous  revision,  bringing 
this  edition  right  down  to  the  minute.  Important  new  additions  have  increased  it 
in  size  some  180  pages,  By  far  the  most  important  addition  is  the  inclusion  of 
an  entirely  new  section  on  Pathoge7iic  Protozoa.  This  section  considers  every 
protozoan  pathogenic  to  man  ;  and  in  that  same  clean-cut,  definite  way  that  won 
for  McFarland' s  work  a  place  in  the  very  front  of  medical  bacteriologies.  The 
illustrations  are  the  best  the  world  affords,  and  are  beautifully  executed. 

H.  B.  Anderson,  M.  D., 

Professor  of  Pathology  and  Bacteriology,   Trinity  Medical  College,  Toronto. 
"  The  book  is  a  satisfactory  one,  and  I  shall  take  pleasure  in  recommending  it  to  the  students 
of  Trinity  College." 

The  Lancet,  London 

"  It  is  excellently  adapted  for  the  medical  students  and  practitioners  for  whom  it  is  avowedly 
written.  .  .  .  The  descriptions  given  are  accurate  and  readable  " 

Hill's  Histology  and  Organography 

A  Manual  of  Histology  and  Organography.  By  Charles  Hill, 
M.  D.,  formerly  Assistant  Professor  of  Histology  and  Embryology, 
Northwestern  University,  Chicago.  i2mo  of  483  pages,  337  illustra- 
tions.    Cloth,  ;^2.2  5  net. 

THE    NEW    (3d)   EDITION 

Dr.  Hill's  work  is  characterized  by  a  completeness  of  discussion  rarely  met  in 
a  book  of  this  size.      Particular  consideration  is  given  the  mouth  and  teeth. 

Pennsylvania  Medical  Journal 

"  It  is  arranged  in  such  a  manner  as  to  be  easy  of  access  and  comprehension.  To  anj 
contemplating  the  study  of  histology  and  organography  we  would  commend  this  work." 


SAUNDERS'    BOOKS   ON 


GET  ifc     •  THE  NEW 

THE  BEST  /\  111  C  r  1  C  8i  II  STANDARD 

Illustrated   Dictionary 

Just  Out— New  (8th)  Edition— 150O  New  Terms 


The  American  Illustrated  Medical  Dictionary.  A  new  and  com- 
plete dictionary  of  the  terms  used  in  Medicine,  Surgery,  Dentistry, 
Pharmacy,  Chemistry,  Veterinary  Science,  Nursing,  and  kindred 
branches ;  with  over  100  new  and  elaborate  tables  and  many  handsome 
illustrations.  By  W.  A.  Newman  Borland,  M.D.,  Editor  of  "The 
American  Pocket  Medical  Dictionary."  Large  octavo,  1 137  pages, 
bound  in  full  flexible  leather.  Price,  ^4.50  net;  with  thumb  index, 
$5.00  net. 

IT  DEFINES  ALL  THE  NEW  WORDS— IT  IS  UP  TO  DATE 

The  American  Illustrated  Medical  Dictionary  defines  hundreds  of  the  newest 
terms  not  defined  in  any  other  dictionary — bar  none.  These  new  terms  are  live, 
active  words,  taken  right  from  modern  medical  literature. 

It  gives  the  capitalization  and  pronunciation  of  all  words.  It  makes  a  feature 
of  the  derivation  or  etymology  of  the  words.  In  some  dictionaries  the  etymology 
occupies  only  a  secondary  place,  in  many  cases  no  derivation  being  given  at  all. 
In  the  American  Illustrated  practically  every  word  is  given  its    derivation. 

Every  word  has  a  separate  paragraph,  thus  making  it  easy  to  find  a  word 
quickly. 

The  tables  of  arteries,  muscles,  nerves,  veins,  etc.,  are  of  the  greatest  help  in 
assembling  anatomic  facts.  In  them  are  classified  for  quick  study  all  the  neces- 
sary information  about  the  various  structures. 

Every  word  is  given  its  definition — a  definition  that  defines  in  the  fewest  pos- 
sible words.  In  some  dictionaries  hundreds  of  words  are  not  defined  at  all, 
referring  the  reader  to  some  other  source  for  the  information  he  wants  at  once. 

Howard  A,  Kelly,  M.  Yi,,  Johns  Hopkins  University,  Baltimore. 

■■  The  American  Illustrated  Dictionary  is  admirable.  It  is  so  well  gotten  up  and  of  such 
convenient  size.     No  errors  have  been  found  in  my  use  of  it." 

J.  Collins  Warren,  M.  D.,  LL.D.,  F.R.C.S.  (Hon.),  Harvard  Medical  School 

"  I  regard  it  as  a  valuable  aid  to  my  medical  literary  work.  It  is  very  complete  and  of 
convenient  size  to  handle  comfortably.     I  use  it  in  preference  to  any  other." 


PATHOLOGY 


Stengel  O  Fox's  Pathology 

Pathology.  By  Alfred  Stengel,  M.  D.,  Sc.  D.,  Professor  of  Medi- 
cine, University  of  Pennsylvania;  and  Herbert  Fox,  M.  D.,  Director 
of  the  Pepper  Laboratories  of  Clinical  Medicine,  University  of  Pennsyl- 
vania. Octavo  of  1045  pages,  with  468  text-illustrations,  many  in 
colors,  and  1 5  colored  plates.     Cloth,  g6.oo  net ;  Half  Morocco,  $7.50  net. 

JUST   READY— NEW  (6th)  EDITION,   REWRITTEN 

This  new  (6th)  edition  is  virtually  a  new  work.  It  has  been  rewritten  through- 
out, reset  in  new  type,  and  a  larger  type  page  used.  New  matter  equivalent  to 
175  pages  has  been  added  and  some  75  new  ilhistrations,  many  of  them  in  colors. 
The  work  is  a  handsome  volume  of  over  1000  pages.  In  the  first  portions,  de- 
voted to  general  pathology,  the  sections  on  inflammation,  retrogressive  processes, 
disorders  of  nutrition  and  metabolism,  general  etiology,  and  diseases  due  to  bac- 
teria were  wholly  rewritten  or  very  largely  recast.  A  new  section  on  transmissible 
diseases  was  added ;  the  terata  were  included,  with  a  synoptical  chapter  on  terat- 
ology. The  glands  of  internal  secretion  were  given  a  separate  chapter,  and  new 
chapters  on  the  pathology  of  eye,  ear,  and  skin  ^txe,  added. 


Stiles  on  the  Nervous  System 

The  Nervous  System  and  its  Conservation.  By  Percy  G. 
Stiles,  Instructor  in  Physiology  at  Harvard  University.  i2mo  of  230 
pages,  illustrated.     Cloth,  ^1.25  net. 

ILLUSTRATED 

You  get  chapters  on  the  minute  structure,  elements  of  nerve  physiology,  re- 
flexes, anatomy,  afferent  nervous  system,  neuromuscular  system  and  fatigue, 
autonomic  system,  the  cerebrum  and  human  development,  emotion,  sleep,  dreams, 
causes  of  nervous  impairment,  neurasthenia,  hygiene. 


Stiles'  Nutritional  Physiology 

Nutritional  Physiology.  By  Percy  Goldthwait  Stiles,  In- 
structor in  Physiology  at  Harvard  University.  i2mo  of  295  pages, 
illustrated.     Cloth,  ^1.25  net. 

ILLUSTRATED 

This  new  work  expresses  the  most  advanced  views  on  this  important  subject. 
It  discusses  in  a  concise  way  the  processes  of  digestion  and  metabolism.  The 
key-word  of  the  book  throughout  is  "  energy  " — its  source  and_its  conservation. 

"  It  is  remarkable  for  the  fineness  of  its  diction  and  for  its  clear  presentation  of  the  sub- 
ject, relieved  here  and  there  by  a  quaintly  humorous  turn  of  phrase  that  is  altogether  delight- 
ful."— Colin  C.  Stewart,  Ph.  £>.,  Dartmouth  College, 


SAUNDERS'    BOOKS   ON 


Jordan's 
General    Bacteriology 

A  Text=Book  of  General  Bacteriology.  By  Edwin  O.  Jordan,  Ph.D., 
Professor  of  Bacteriology  in  the  University  of  Chicago  and  in  Rush 
Medical  College.     Octavo  of  650  pages,  illustrated.     Cloth,  ^3.00  net. 

NEW  (4th)  EDITION 

Professor  Jordan's  work  embraces  the  entire  field  of  bacteriology,  the  non- 
pathogenic as  well  as  the  pathogenic  bacteria  being  considered,  giving  greater 
emphasis,  of  course,  to  the  latter.  There  are  extensive  chapters  on  methods  of 
studying  bacteria,  including  staining,  biochemical  tests,  cultures,  etc. ;  on  the 
development  and  composition  of  bacteria  ;  on  enzymes  and  fermentation-products; 
on  the  bacterial  production  of  pigment,  acid  and  alkali  ;  and  on  ptomains  and 
toxins.  Especially  complete  is  the  presentation  of  the  serum  treatment  of  gonor- 
rhea, diphtheria,  dysentery,  and  tetanus.  The  relation  of  bovine  to  human 
tuberculosis  and  the  ocular  tuberculin  reaction  receive  extensive  consideration. 

This  work  will  also  appeal  to  academic  and  scientific  students.  It  contains 
chapters  on  the  bacteriology  of  plants,  milk  and  milk-products,  air,  agriculture, 
water,  food  preservatives,  the  processes  of  leather  tanning,  tobacco  curing,  and 
vinegar  making  ;  the  relation  of  bacteriology  to  household  administration  and  to 
sanitary  engineering,  etc. 

Prof.  Severance  Burra^e,  Associate  Professor  0/  Sanitary  Science,  Purdue  University. 

"  I  am  much  impressed  with  the  completeness  and  accuracy  of  the  book.  It  certainly 
covers  the  ground  more  completely  than  any  other  American  book  that  I  have  seen." 


Buchanan's 
Veterinary   Bacteriology 

Veterinary  Bacteriology.     By  Robert  E.  Buchanan,  Ph.D.,  Pro- 
fessor of  Bacteriology  in  the  Iowa  State  College  of  Agriculture  and 
Mechanic  Arts.     Octavo,  5 16  pages,  2 14  illustrations.     Cloth,  ^3.00  net. 
THE  BEST  PUBLISHED 

Professor  Buchanan  discusses  thoroughly  all  bacteria  causing  diseases  of  the 
domestic  animals.  He  goes  minutely  into  the  consideration  of  immunity,  opsonic 
index,  reproduction,  sterilization,  antiseptics,  biochemic  tests,  culture-media, 
isolation  of  cultures,  the  manufacture  of  the  various  toxins,  antitoxins,  tuberculins, 
and  vaccines  that  have  proved  of  diagnostic  or  therapeutic  value.  Then,  in  addi- 
tion to  bacteria  and  protozoa  proper,  he  considers  molds,  mildews,  smuts,  rusts, 
toadstools,  puff"-balls,  and  the  other  fungi  pathogenic  for  animals. 
B.  F.  Kaupp,  D.  V.  S.»  State  AgricicUural  College,  Fort  Collins. 

"  It  is  the  best  in  print  on  the  subject.     What  pleases  me  most  is  that  it  contains  all  the  late 
results  of  research.     It  fills  a  long  felt  want," 


EMBRYOLOGY. 


Heisler's  Embryology 

A  Text=Book  of  Embryology.  By  John  C.  Heisler,  M.  D.,  Pro- 
fessor of  Anatomy  in  the  Medico-Chirurgical  College,  Philadelphia. 
Octavo  volume  of  435  pages,  with  212  illustrations,  32  of  them  in 
colors.     Cloth,  ^3.00  net. 

THIRD  EDITION— WITH  212  ILLUSTRATIONS,  32  IN  COLORS 

This  edition  represents  all  the  advances  recently  made  in  the  science  of  em- 
bryology. Many  portions  have  been  entirely  rewritten,  and  a  great  deal  of  new 
and  important  matter  added.  A  number  01  new  illustrations  have  also  been  intro- 
duced and  these  will  prove  very  valuable.  Heisler' s  Embryology  has  become 
a  standard  work. 

G.  Carl  Huber.  M.  D.. 

Professor  of  Embryology  at  the  Wistar  Institute,  University  of  Pennsytania. 
"  I  find  this  edition  of    'A  Text-Book  of  Embryology,'  by  Dr.   Heisler,  an  improvement 
on  the  former  one.     The  figures  added  increase  greatly   the   value  of  the  work.     I   am   again 
recommending  it  to  our  students." 


Bohm,   Davidoff,  and 
Huberts   Histology 

A  Text=Book  of  Human  Histology.  Including  Microscopic  Tech- 
nic.  By  Dr.  A.  A.  Bohm  and  Dr.  M.  Vox  Davidoff,  of  Munich,  and 
G.  Carl  Huber,  M.  D.,  Professor  of  Embryology  at  the  Wistar  Insti- 
tute, University  of  Pennsylvania.  Handsome  octavo  of  528  pages,  with 
361  beautiful  original  illustrations.      Flexible  cloth,  $^.$0  net. 

SECOND  EDITION,  ENLARGED 

The  work  of  Drs.  Bohm  and  Davidoff  is  well  known  in  the  German  edition, 
and  has  been  considered  one  of  the  most  practically  useful  books  on  the  subject 
of  Human  Histology.  This  second  edition  has  been  in  great  part  rewritten  and 
very  much  enlarged  by  Dr.  Huber,  who  has  also  added  over  one  hundred  original 
illustrations.  Dr.  Huber' s  extensive  additions  have  rendered  the  work  the  most 
complete  students'  text-book  on  Histology  in  existence. 

Boston  Medical  and  Surgical  Journal 

"  Is  unquestionably  a  lext-book  of  the  first  rank,  having  been  carefully  written  by  thorough 
masters  of  the  subject,  and  in  certain  directions  it  is  much  superior  to  any  other  histological 
manual." 


SAUNDERS'    BOOKS   ON 


Wells'  Chemical  Pathology 


Chemical  Pathology. — Being  a  Discussion  of  General  Pathology 
from  the  Standpoint  of  the  Chemical  Processes  Involved.  By  H. 
Gideon  Wells,  Ph.  D.,  M.  D.,  Assistant  Professor  of  Pathology  in  the 
University  of  Chicago.     Octavo  of  6i6  pages.     Cloth,  ^3. 25  net. 

NEW  (2d)  EDITION 

Dr.  Wells'  work  is  written  for  the  physician,  for  those  engaged  in  research  in 
pathology  and  physiologic  chemistry,  and  for  the  medical  student.  In  the  intro- 
ductory chapter  are  discussed  the  chemistry  and  physics  of  the  animal  cell,  giving 
the  essential  facts  of  ionization,  diffusion,  osmotic  pressure,  etc.,  and  the  relation 
of  these  facts  to  cellular  activities.  Special  chapters  are  devoted  to  Diabetes  and 
to  Uric-acid  Metabolism  and  Gout. 

Wm.   H.  Welch.   M.  D. 

Professor  of  Pathology ,  Johns  Hopkins  University. 

"  The  work  fills  a  real  need  in  the  English  hterature  of  a  very  important  subject,  and  I 
shall  be  glad  to  recommend  it  to  my    students." 

Lusk's 
Clements  of  Nutrition 

Elements  of  the  Science  of  Nutrition.  By  Graham  Lusk,  Ph.  D., 
Professor  of  Physiology  at  Cornell  Medical  School.  Octavo  volume 
of  302  pages.     Cloth,  ^3.00  net. 

THE  NEW  (2d)  EDITION— TRANSLATED  INTO  GERMAN 

Prof.  Lusk  presents  the  scientific  foundations  upon  which  rests  our  knowledge 
of  nutrition  and  metabolism,  both  in  health  and  in  disease.  There  are  special 
chapters  on  the  metabolism  of  diabetes  and  fever,  and  on  purin  metabolism. 
The  work  will  also  prove  valuable  to  students  of  animal  dietetics  at  agricultural 
stations. 

Lewellys  F.  Barker,  M.  D. 

Professor  of  the  Principles  and  Practice  of  Medicine,  Johns  Hopkins  University. 
"  I  shall  recommend  it  highly  to  my  students.     It  is  a  comfort  to  have  such  a  discussion 
of  the  subject  in  English." 


HISTOLOGY. 


Daugherty's 
Economic   Zoology 

Economic  Zoology.  By  L.  S.  Daugherty,  M.  S.,  Ph.  D.,  Professor 
of  Zoology,  State  Normal  School,  Kirksville,  Mo.,  and  M.  C.  Daugh- 
erty, author  with  Jackson  of  "  Agriculture  Through  the  Laboratory 
and  School  Garden."  Part  I:  Field  atid  Laboratory  Gtiide.  i2mo  of 
237  pages,  interleaved.  Cloth,  ^1.25  net.  Part  II:  Principles.  l2mo 
of  406  pages,  illustrated.  Cloth,  $2.00  net. 
ILLUSTRATED 


There  is  no  other  book  just  like  this.  Not  only  does  it  give  the  salient  facts 
of  structural  zoology  and  the  development  of  the  various  branches  of  animals,  but 
also  the  natural  history — the  life  and  habits — thus  showing  the  interrelations  of 
structure,  habit,  and  environment.  In  a  word,  it  gives  the  principles  of  zoology 
and  their  actual  application.  The  economic  phase  is  emphasized. 
Part  I — the  Field  and  Laboratory  Guide — is  designed  for  practical  instruction  in 
the  field  and  laboratory.  To  enhance  its  value  for  this  purpose  blank  pages  arc 
inserted  for  notes. 


DrewV 

Invertebrate  Zoology 

A  Laboratory  Manual  of  Invertebrate  Zoology.  By  Oilman  A. 
Drew,  Ph.D.,  Assistant  Director  at  Marine  Biological  Laboratory,  Woods 
Hole,  Mass.  With  the  aid  of  Former  and  Present  Members  of  the  Zoological 
Staff  of  Instructors.     i2mo  of  213  pages.  Cloth,  gi.25  net. 

NEW  (2d)  EDITION 

The  subject  is  presented  in  a  logical  way,  and  the  type  method  of  study  has 
been  followed,  as  this  method  has  been  the  prevailing  one  for  many  years. 

Prof.  Allison  A.  Smyth,  Jr.,  N^rginia  Polytechnic  Institute 

"  I  think  it  is  the  best  laboratory  manual  of  zoology  I  have  yet  seen.  The  large  number 
of  forms  dealt  with  makes  the  work  applicable  to  almost  any  locality." 


SAUNDERS    BOOKS    ON 


Norris*   Cardiac   Pathology 

Studies  in  Cardiac  Pathology.  By  George  W.  Norris,  M.D., 
Associate  in  Medicine  at  the  University  of  Pennsylvania.  Large  octavo 
of  235  pages,  with  85  superb  illustrations.     Cloth,  ^5.00  net. 

SUPERB    ILLUSTRATIONS 

The  illustrations  are  superb.     Each  illustration  is  accompanied  by  a  detailed 
description;  besides,  there  is  ample  letter  press  supplementing  the  pictures. 

Boston  Medical  and  Surgical  Journal 

"  The  illustrations  are  arranged  in  such  a  way  as  to  illustrate  all  the  common  and  many  of 
the  rare  cardiac  lesions,  and  the  accompanying  descriptive  text  constitutes  a  fairly  continuous 
didactic  treatise." 


McConneirs  Pathology 

A  Manual  of  Pathology.  By  Guthrie  McConnell,  M.  D.,  As- 
sistant Surgeon,  Medical  Reserve  Corps,  U.  S.  Navy.  i2mo  of  523 
pages,  with  170  illustrations.     Flexible  leather,  $2.50  net. 

NEW  (2d)  EDITION 

Dr.  McConnell  has  discussed  his  subject  with  a  clearness  and  precision  of 
style  that  make  the  work  of  great  assistance  to  both  student  and  practitioner. 
The  illustrations  have  been  introduced  for  their  practical  value. 

New  York  State  Journal  of  Medicine 

"  The  book  treats  the  subject  of  pathology  with  a  thoroughness  lacking  in  many  works  of 
greater  pretension.  The  illustrations — many  of  them  original — are  profuse  and  of  exceptional 
excellence." 


McConnell's  Pathology  and  Bacteriology  ''°s.uda"n?] 

Pathology  and  Bacteriology  for  Dental  Students.  By  Guthrie 
McConnell,  M.  D.,  Assistant  Surgeon,  Medical  Reserve  Corps,  U.  S.  N. 
i2mo  of  309  pages,  illustrated.      Cloth,  ^2.25  net. 

ILLUSTRATED 

This  work  is  written  expressly  for  dentists  and  dental  students,  emphasizing 
throughout  the  application  of  pathology  and  bacteriology  in  dental  study  and  prac- 
tice. There  are  chapters  on  disorders  of  metabolism  and  circulation;  retro- 
gressive processes,  cell  division  inflammation  and  regeneration,  granulomas,  pro- 
gressive processes,  tumors,  special  mouth  pathology,  sterilization  and  disinfection, 
bacteriologic  methods,  specific  micro-organisms,  infection  and  immunity,  and 
laboratory  technic. 


HISTOLOGY. 


Dtirck  and  Hektoen's 

Special    Pathologic    Histology 

Atlas  and  Epitome  of  Special  Pathologic  Histology.     By  Dr.  H. 

DURCK,  of  Munich.  Edited,  with  additions,  by  Ludvig  Hektoen,  M.  D., 
Professor  of  Pathology,  Rush  Medical  College,  Chicago.  In  two  parts. 
Part  I. — Circulatory,  Respiratoiy,  and  Gastro-intestinal  Tracts.  120 
colored  figures  on  62  plates,  and  158  pages  of  text.  Part  II. — Liver, 
Urinary  and  Sexual  Organs,  Nervous  System,  Skin,  Muscles,  and 
Bones.  123  colored  figures  on  60  plates,  and  192  pages  of  text.  Per 
part :   Cloth,  ^^3.00  net.     In  Saimders'  Hand-Atlas  Series. 

The  great  value  of  these  plates  is  that  they  represent  in  the  exact  colors  the  effect 
of  the  stains,  which  is  of  such  great  importance  for  the  differentiation  of  tissue. 
The  text  portion  of  the  book  is  admirable,  and,  while  brief  it  is  entirely  satisfac- 
tory in  that  the  leading  facts  are  stated,  and  so  stated  that  the  reader  feels  he  has 
grasped  the  subject  e.xtensively. 

William  H.  Welch,  M.  D., 

Proft'ssor  of  Pathology,  Joktis  Hopkins  University,  Baltimore. 

"  I  consider  Diirck's  '  Atlas  of  Special  Pathologic  Histology,'  edited  by  Hektoen.  a  very 
useful  book  for  students  and  others.     The  plates  are  admirable." 

Sobotta  and  Huber's 
Human  Histology 

Atlas  and  Epitome  of  Human  Histology.  By  Privatdocent  Dr. 
J.  Sobotta,  of  Wijrzburg.  Edited,  with  additions,  by  G.  Carl  Huber, 
M.  D.,  Professor  of  Histology  and  Embryology  in  the  University  of 
Michigan,  Ann  Arbor.  With  214  colored  figures  on  ?,o  plates,  68 
text-illustrations,  and  248  pages  of  text.  Cloth,  ^4.50  net.  In 
Saunders'  Hand-Atlas  Series. 

INCLUDING   MICROSCOPIC  ANATOMY 

The  work  combines  an  abundance  of  well-chosen  and  most  accurate  illustra- 
tions, with  a  concise  te.\t,  and  in  such  a  manner  as  to  make  it  both  atlas  and  text- 
book. The  great  majority  of  the  illustrations  were  made  from  sections  prepared 
from  human  tissues,  and  always  from  fresh  and  in  every  respect  normal  specimens. 
The  colored  lithographic  plates  have  been  produced  with  the  aidof  over  thirty  colors. 

Boston  Medical  and  Surgical  Journal 

"In  color  and  proportion  they  are  characterized  by  gratifying  accuracy  and  lithographic 
beauty." 


14  SAUNDERS    BOOKS    ON 

Bosanquet  on  Spirochaetes 

Spirochsetes :  A  Review  of  Recent  Work,  with  Some  Original  Ob- 
servations. By  W.  Cecil  Bosanquet,  M.D.,  Fellow  of  the  Royal  Col- 
lege of  Physicians,  London.    Octavo  of  1 52  pages,  illustrated.  ^2.50  net. 

ILLUSTRATED 

This  is  a  complete  and  authoritative  monograph  on  the  spirochsetes,  giving 
morphology,  pathogenesis,  classification,  staining,  etc.  Pseudospirocheetes  are 
also  considered,  and  the  entire  text  well  illustrated.  The  high  standing  of  Dr. 
Bosanquet  in  this  field  of  study  makes  this  new  work  particularly  valuable. 


Levy  and  Klemperer's 
Clinical  Bacteriology 

The  Elements  of  Clinical  Bacteriology.  By  Drs.  Ernst  Levy  and 
Felix  Klemperee,  of  the  University  of  Strasburg.  Translated  and 
edited  by  Augustus  A.  Eshner,  M.  D.,  Professor  of  Clinical  Medicine, 
Philadelphia  Polyclinic.  Octavo  volume  of  440  pages,  fully  illustrated. 
Cloth,  ^2.50  net. 

S.  Solis-Cohen,  M.  D., 

Professor  of  .Clinical  Medicine,  Jefferson  Medical  College,  Philadelphia. 
"  I  consider  it  an  excellent  book.     I  have  recommended  it  in  speaking  to  my  students." 


Lehmann,  Neumann,  and 
Weaver's  Bacteriology 

Atlas  and  Epitome  of  Bacteriology :  including  a  Text-Book  of 
Special  Bacteriologic  Diagnosis.  By  Prof.  Dr.  K.  B.  Lehmann 
and  Dr.  R.  O.  Neumann,  of  Wiirzburg.  From  the  Second  Revised  and 
Enlarged  German  Edition.  Edited,  with  additions,  by  G.  H.  Weaver, 
M.  D.,  Assistant  Professor  of  Pathology  and  Bacteriology,  Rush  Medical 
College,  Chicago.  In  two  parts.  Part  I. — 632  colored  figures  on  69 
lithographic  plates.  Part  II. — 511  pages  of  text,  illustrated.  Per  part: 
Cloth,  ^2.50  net.     In  Saunders'  Hand-Atlas  Series. 


PATHOLOGY,  BACTERIOLOGY,  AND   PATHOLOGY  15 

Durck  and  Hektoen's  General  Pathologic  Histology 

Atlas  and  Epitome  of  General  Pathologic  Histology.  By  Pr. 
Dr.  H.  Durck,  of  Munich.  Edited,  with  additions,  by  Ludvig  Hek- 
toen,  M.  D.,  Professor  of  Pathology  in  Rush  Medical  College,  Chicago. 
172  colored  figures  on  77  lithographic  plates,  36  text-cuts,  many 
in  colors,  and  353  pages.  Cloth,  55.00  net.  Lt  Saunders'' Hand- Atlas 
Series. 

American  Text-Book  of  Physiology  second  Edition 

American  Text-Book  of  Physiology.  In  two  volumes.  Edited  by 
William  H.  Howell,  Ph.  D.,  M.D.,  Professor  of  Physiology  in  the  Johns 
Hopkins  University,  Baltimore,  Md.  Two  royal  octavos  of  about  600 
pages  each,  illustrated.  Per  volume:  Cloth,  ^3. 00  net;  Half  Morocco, 
114.25  net. 

"  The  work  will  stand  as  a  work  of  reference  on  physiology.  To  him  who  desires  to  know 
the  status  of  modern  physiology,  who  expects  to  obtain  suggestions  as  to  further  physio- 
logic inquiry,  we  know  of  none  in  English  which  so  eminently  meets  such  a  demand." — 

The  Medical  News, 

Warren's  Pathology  and  Therapeutics        second  Edition 

Surgical  Pathology  and  Therapeutics.  By  John  Collins  Warren, 
M.  D.,  LL.D.,  F.  R.  C.  S.  (Hon.),  Professor  of  Surgery,  Harvard  Med- 
ical School.  Octavo,  873  pages,  136  relief  and  lithographic  illustrations, 
33  in  colors.  With  an  Appendix  on  Scientific  Aids  to  Surgical  Diagnosis 
and  a  series  of  articles  on  Regional  Bacteriology.  Cloth,  55.00  net; 
Half  Morocco,  56-5°  net. 

Raymond's  Physiology  New  (3d)  Edition 

Human  Physiology.  By  Joseph  H.  Raymond,  A.  M.,  M.  D.,  Pro- 
fessor of  Physiology  and  Hygiene,  Long  Island  College  Hospital,  New 
York.     Octavo  of  685  pages,  with  444  illustrations.     Cloth,  53. 50  net. 

"  The  book  is  well  gotten  up  and  well  printed,  and  may  be  regarded  as  a  trustworthy 
guide  for  the  student  and  a  useful  work  of  reference  for  the  general  practitioner.  The 
illustrations  are  numerous  and  are  well  executed." — The  Lancet,  London. 


l6  BACTERIOLOGY,    PHYSIOLOGY,    AND   HISTOLOGY. 

Ball's    BaCteriolO^  seventh  Edition,  Revised 

Essentials  of  Bacteriology  :  being  a  concise  and  systematic  intro- 
duction to  tlie  Study  of  Micro-organisms.  By  M.  V.  Ball,  M.  D.,  Late 
Bacteriologist  to  St.  Agnes'  Hospital,  Philadelphia.  i2mo  of  289  pages, 
with  135  illustrations,  some  in  colors.  Cloth,  Ji.oo  net.  In  Saunders' 
Questiofi-  Compend  Series. 

"  The  technic  with  regard  to  media,  staining,  mounting,  and  the  lil<e  is  culled  from  the 
latest  authoritative  works." — T/ie  Medical  Times,  New  Yorli. 

Bud£(ett'S    Physiology  New  (3d)  EditJon 

Essentials  of  Physiology.  Prepared  especially  for  Students  of  Medi- 
cine, and  arranged  with  questions  following  each  chapter.  By  Sidney 
P.  Budgett,  M.  D.,  formerly  Professor  of  Physiology,  Washington  Uni- 
versity, St.  Louis.  Revised  by  Havan  Emerson,  M.  D.,  Demonstratoi 
of  Physiology,  Columbia  University,  izmo  volume  of  250  pages,  illus- 
trated.    Cloth,  ^ 1. 00  net.     Sauridcrs'  Question- Compend  Se>-ies, 

"He  has  an  excellent  conception  of  his  subject.  .  .  It  is  one  of  the  most  satisfactory 
books  of  this  class" — University  of  Pennsylvania  Medical  Bulletin. 

Leroy's  Histology  New  (4th)  Edition 

Essentials  of  Histology.  By  Louis  Leroy,  M.  D.,  Professor  of 
Histology  and  Pathology,  Vanderbilt  University,  Nashville,  Tennessee. 
i2mo,  263  pages,  with  92  original  illustrations.  Cloth,  gi.oo  net.  In 
Saunders'  Question-  Conipe?id  Series. 

"  The  work  in  its  present  form  stands  as  a  model  of  what  a  student's  aid  should  be  ;  and 
we  unhesitatingly  say  that  the  practitioner  as  well  would  find  a  glance  through  the  book 
of  lasting  benefit." — T/ie  Medical  World,  Philadelphia. 

Barton  and  Wells*  Medical  Thesaurus 

A  Thesaurus  of  Medical  Words  and  Phrases.  By  Wilfred  M. 
Barton,  M.  D.,  Assistant  Professor  of  Materia  Medica  and  Therapeutics, 
and  Walter  A.  Wells,  M.D.,  Demonstrator  of  Laryngology,  Georgetown 
University,  AVashington,  D.  C.  i2mo,  534  pages.  Flexible  leather, 
^2.50  net;  thumb  indexed,  $3.00  net. 

American  Pocket  Medical  Dictionary       ^^^  (p^j,)  Edition 

American  Pocket  Medical  Dictionary.  Edited  by  W.  A.  New- 
man DoRLAND,  M.  D.,  Editor  "American  Illustrated  Medical  Dic- 
tionary." Containing  the  pronunciation  and  definition  of  the  principal 
words  used  in  medicine  and  kindred  sciences,  with  75  extensive  tables. 
693  pages.  Flexible  leather,  with  gold  edges,  ^i.oo  net;  with  patent 
thumb  index,  ^1.25  net. 

"I  can  recommend  it  to  our  students  without  reserve." — J.  H.  HOLL.\ND,  M..  D.,  of 
the  Jefferson  Medical  College,  Philadelphia. 


